IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000000000309
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4535G>T (p.Ser1512Ile)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Benign
Aug 2015 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.4535G>T (p.Ser1512Ile)
Variation ID: 41826 Accession: VCV000041826.103
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43074471 (GRCh38) [ NCBI UCSC ] 17: 41226488 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 12, 2013 Oct 20, 2024 Aug 10, 2015 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4535G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ser1512Ile missense NM_001407571.1:c.4322G>T NP_001394500.1:p.Ser1441Ile missense NM_001407581.1:c.4601G>T NP_001394510.1:p.Ser1534Ile missense NM_001407582.1:c.4601G>T NP_001394511.1:p.Ser1534Ile missense NM_001407583.1:c.4598G>T NP_001394512.1:p.Ser1533Ile missense NM_001407585.1:c.4598G>T NP_001394514.1:p.Ser1533Ile missense NM_001407587.1:c.4598G>T NP_001394516.1:p.Ser1533Ile missense NM_001407590.1:c.4595G>T NP_001394519.1:p.Ser1532Ile missense NM_001407591.1:c.4595G>T NP_001394520.1:p.Ser1532Ile missense NM_001407593.1:c.4535G>T NP_001394522.1:p.Ser1512Ile missense NM_001407594.1:c.4535G>T NP_001394523.1:p.Ser1512Ile missense NM_001407596.1:c.4535G>T NP_001394525.1:p.Ser1512Ile missense NM_001407597.1:c.4535G>T NP_001394526.1:p.Ser1512Ile missense NM_001407598.1:c.4535G>T NP_001394527.1:p.Ser1512Ile missense NM_001407602.1:c.4535G>T NP_001394531.1:p.Ser1512Ile missense NM_001407603.1:c.4535G>T NP_001394532.1:p.Ser1512Ile missense NM_001407605.1:c.4535G>T NP_001394534.1:p.Ser1512Ile missense NM_001407610.1:c.4532G>T NP_001394539.1:p.Ser1511Ile missense NM_001407611.1:c.4532G>T NP_001394540.1:p.Ser1511Ile missense NM_001407612.1:c.4532G>T NP_001394541.1:p.Ser1511Ile missense NM_001407613.1:c.4532G>T NP_001394542.1:p.Ser1511Ile missense NM_001407614.1:c.4532G>T NP_001394543.1:p.Ser1511Ile missense NM_001407615.1:c.4532G>T NP_001394544.1:p.Ser1511Ile missense NM_001407616.1:c.4532G>T NP_001394545.1:p.Ser1511Ile missense NM_001407617.1:c.4532G>T NP_001394546.1:p.Ser1511Ile missense NM_001407618.1:c.4532G>T NP_001394547.1:p.Ser1511Ile missense NM_001407619.1:c.4532G>T NP_001394548.1:p.Ser1511Ile missense NM_001407620.1:c.4532G>T NP_001394549.1:p.Ser1511Ile missense NM_001407621.1:c.4532G>T NP_001394550.1:p.Ser1511Ile missense NM_001407622.1:c.4532G>T NP_001394551.1:p.Ser1511Ile missense NM_001407623.1:c.4532G>T NP_001394552.1:p.Ser1511Ile missense NM_001407624.1:c.4532G>T NP_001394553.1:p.Ser1511Ile missense NM_001407625.1:c.4532G>T NP_001394554.1:p.Ser1511Ile missense NM_001407626.1:c.4532G>T NP_001394555.1:p.Ser1511Ile missense NM_001407627.1:c.4529G>T NP_001394556.1:p.Ser1510Ile missense NM_001407628.1:c.4529G>T NP_001394557.1:p.Ser1510Ile missense NM_001407629.1:c.4529G>T NP_001394558.1:p.Ser1510Ile missense NM_001407630.1:c.4529G>T NP_001394559.1:p.Ser1510Ile missense NM_001407631.1:c.4529G>T NP_001394560.1:p.Ser1510Ile missense NM_001407632.1:c.4529G>T NP_001394561.1:p.Ser1510Ile missense NM_001407633.1:c.4529G>T NP_001394562.1:p.Ser1510Ile missense NM_001407634.1:c.4529G>T NP_001394563.1:p.Ser1510Ile missense NM_001407635.1:c.4529G>T NP_001394564.1:p.Ser1510Ile missense NM_001407636.1:c.4529G>T NP_001394565.1:p.Ser1510Ile missense NM_001407637.1:c.4529G>T NP_001394566.1:p.Ser1510Ile missense NM_001407638.1:c.4529G>T NP_001394567.1:p.Ser1510Ile missense NM_001407639.1:c.4529G>T NP_001394568.1:p.Ser1510Ile missense NM_001407640.1:c.4529G>T NP_001394569.1:p.Ser1510Ile missense NM_001407641.1:c.4529G>T NP_001394570.1:p.Ser1510Ile missense NM_001407642.1:c.4529G>T NP_001394571.1:p.Ser1510Ile missense NM_001407644.1:c.4526G>T NP_001394573.1:p.Ser1509Ile missense NM_001407645.1:c.4526G>T NP_001394574.1:p.Ser1509Ile missense NM_001407646.1:c.4523G>T NP_001394575.1:p.Ser1508Ile missense NM_001407647.1:c.4520G>T NP_001394576.1:p.Ser1507Ile missense NM_001407648.1:c.4478G>T NP_001394577.1:p.Ser1493Ile missense NM_001407649.1:c.4475G>T NP_001394578.1:p.Ser1492Ile missense NM_001407652.1:c.4535G>T NP_001394581.1:p.Ser1512Ile missense NM_001407653.1:c.4457G>T NP_001394582.1:p.Ser1486Ile missense NM_001407654.1:c.4457G>T NP_001394583.1:p.Ser1486Ile missense NM_001407655.1:c.4457G>T NP_001394584.1:p.Ser1486Ile missense NM_001407656.1:c.4454G>T NP_001394585.1:p.Ser1485Ile missense NM_001407657.1:c.4454G>T NP_001394586.1:p.Ser1485Ile missense NM_001407658.1:c.4454G>T NP_001394587.1:p.Ser1485Ile missense NM_001407659.1:c.4451G>T NP_001394588.1:p.Ser1484Ile missense NM_001407660.1:c.4451G>T NP_001394589.1:p.Ser1484Ile missense NM_001407661.1:c.4451G>T NP_001394590.1:p.Ser1484Ile missense NM_001407662.1:c.4451G>T NP_001394591.1:p.Ser1484Ile missense NM_001407663.1:c.4451G>T NP_001394592.1:p.Ser1484Ile missense NM_001407664.1:c.4412G>T NP_001394593.1:p.Ser1471Ile missense NM_001407665.1:c.4412G>T NP_001394594.1:p.Ser1471Ile missense NM_001407666.1:c.4412G>T NP_001394595.1:p.Ser1471Ile missense NM_001407667.1:c.4412G>T NP_001394596.1:p.Ser1471Ile missense NM_001407668.1:c.4412G>T NP_001394597.1:p.Ser1471Ile missense NM_001407669.1:c.4412G>T NP_001394598.1:p.Ser1471Ile missense NM_001407670.1:c.4409G>T NP_001394599.1:p.Ser1470Ile missense NM_001407671.1:c.4409G>T NP_001394600.1:p.Ser1470Ile missense NM_001407672.1:c.4409G>T NP_001394601.1:p.Ser1470Ile missense NM_001407673.1:c.4409G>T NP_001394602.1:p.Ser1470Ile missense NM_001407674.1:c.4409G>T NP_001394603.1:p.Ser1470Ile missense NM_001407675.1:c.4409G>T NP_001394604.1:p.Ser1470Ile missense NM_001407676.1:c.4409G>T NP_001394605.1:p.Ser1470Ile missense NM_001407677.1:c.4409G>T NP_001394606.1:p.Ser1470Ile missense NM_001407678.1:c.4409G>T NP_001394607.1:p.Ser1470Ile missense NM_001407679.1:c.4409G>T NP_001394608.1:p.Ser1470Ile missense NM_001407680.1:c.4409G>T NP_001394609.1:p.Ser1470Ile missense NM_001407681.1:c.4406G>T NP_001394610.1:p.Ser1469Ile missense NM_001407682.1:c.4406G>T NP_001394611.1:p.Ser1469Ile missense NM_001407683.1:c.4406G>T NP_001394612.1:p.Ser1469Ile missense NM_001407684.1:c.4535G>T NP_001394613.1:p.Ser1512Ile missense NM_001407685.1:c.4406G>T NP_001394614.1:p.Ser1469Ile missense NM_001407686.1:c.4406G>T NP_001394615.1:p.Ser1469Ile missense NM_001407687.1:c.4406G>T NP_001394616.1:p.Ser1469Ile missense NM_001407688.1:c.4406G>T NP_001394617.1:p.Ser1469Ile missense NM_001407689.1:c.4406G>T NP_001394618.1:p.Ser1469Ile missense NM_001407690.1:c.4403G>T NP_001394619.1:p.Ser1468Ile missense NM_001407691.1:c.4403G>T NP_001394620.1:p.Ser1468Ile missense NM_001407692.1:c.4394G>T NP_001394621.1:p.Ser1465Ile missense NM_001407694.1:c.4394G>T NP_001394623.1:p.Ser1465Ile missense NM_001407695.1:c.4394G>T NP_001394624.1:p.Ser1465Ile missense NM_001407696.1:c.4394G>T NP_001394625.1:p.Ser1465Ile missense NM_001407697.1:c.4394G>T NP_001394626.1:p.Ser1465Ile missense NM_001407698.1:c.4394G>T NP_001394627.1:p.Ser1465Ile missense NM_001407724.1:c.4394G>T NP_001394653.1:p.Ser1465Ile missense NM_001407725.1:c.4394G>T NP_001394654.1:p.Ser1465Ile missense NM_001407726.1:c.4394G>T NP_001394655.1:p.Ser1465Ile missense NM_001407727.1:c.4394G>T NP_001394656.1:p.Ser1465Ile missense NM_001407728.1:c.4394G>T NP_001394657.1:p.Ser1465Ile missense NM_001407729.1:c.4394G>T NP_001394658.1:p.Ser1465Ile missense NM_001407730.1:c.4394G>T NP_001394659.1:p.Ser1465Ile missense NM_001407731.1:c.4394G>T NP_001394660.1:p.Ser1465Ile missense NM_001407732.1:c.4391G>T NP_001394661.1:p.Ser1464Ile missense NM_001407733.1:c.4391G>T NP_001394662.1:p.Ser1464Ile missense NM_001407734.1:c.4391G>T NP_001394663.1:p.Ser1464Ile missense NM_001407735.1:c.4391G>T NP_001394664.1:p.Ser1464Ile missense NM_001407736.1:c.4391G>T NP_001394665.1:p.Ser1464Ile missense NM_001407737.1:c.4391G>T NP_001394666.1:p.Ser1464Ile missense NM_001407738.1:c.4391G>T NP_001394667.1:p.Ser1464Ile missense NM_001407739.1:c.4391G>T NP_001394668.1:p.Ser1464Ile missense NM_001407740.1:c.4391G>T NP_001394669.1:p.Ser1464Ile missense NM_001407741.1:c.4391G>T NP_001394670.1:p.Ser1464Ile missense NM_001407742.1:c.4391G>T NP_001394671.1:p.Ser1464Ile missense NM_001407743.1:c.4391G>T NP_001394672.1:p.Ser1464Ile missense NM_001407744.1:c.4391G>T NP_001394673.1:p.Ser1464Ile missense NM_001407745.1:c.4391G>T NP_001394674.1:p.Ser1464Ile missense NM_001407746.1:c.4391G>T NP_001394675.1:p.Ser1464Ile missense NM_001407747.1:c.4391G>T NP_001394676.1:p.Ser1464Ile missense NM_001407748.1:c.4391G>T NP_001394677.1:p.Ser1464Ile missense NM_001407749.1:c.4391G>T NP_001394678.1:p.Ser1464Ile missense NM_001407750.1:c.4391G>T NP_001394679.1:p.Ser1464Ile missense NM_001407751.1:c.4391G>T NP_001394680.1:p.Ser1464Ile missense NM_001407752.1:c.4391G>T NP_001394681.1:p.Ser1464Ile missense NM_001407838.1:c.4388G>T NP_001394767.1:p.Ser1463Ile missense NM_001407839.1:c.4388G>T NP_001394768.1:p.Ser1463Ile missense NM_001407841.1:c.4388G>T NP_001394770.1:p.Ser1463Ile missense NM_001407842.1:c.4388G>T NP_001394771.1:p.Ser1463Ile missense NM_001407843.1:c.4388G>T NP_001394772.1:p.Ser1463Ile missense NM_001407844.1:c.4388G>T NP_001394773.1:p.Ser1463Ile missense NM_001407845.1:c.4388G>T NP_001394774.1:p.Ser1463Ile missense NM_001407846.1:c.4388G>T NP_001394775.1:p.Ser1463Ile missense NM_001407847.1:c.4388G>T NP_001394776.1:p.Ser1463Ile missense NM_001407848.1:c.4388G>T NP_001394777.1:p.Ser1463Ile missense NM_001407849.1:c.4388G>T NP_001394778.1:p.Ser1463Ile missense NM_001407850.1:c.4388G>T NP_001394779.1:p.Ser1463Ile missense NM_001407851.1:c.4388G>T NP_001394780.1:p.Ser1463Ile missense NM_001407852.1:c.4388G>T NP_001394781.1:p.Ser1463Ile missense NM_001407853.1:c.4388G>T NP_001394782.1:p.Ser1463Ile missense NM_001407854.1:c.4535G>T NP_001394783.1:p.Ser1512Ile missense NM_001407858.1:c.4532G>T NP_001394787.1:p.Ser1511Ile missense NM_001407859.1:c.4532G>T NP_001394788.1:p.Ser1511Ile missense NM_001407860.1:c.4532G>T NP_001394789.1:p.Ser1511Ile missense NM_001407861.1:c.4529G>T NP_001394790.1:p.Ser1510Ile missense NM_001407862.1:c.4334G>T NP_001394791.1:p.Ser1445Ile missense NM_001407863.1:c.4409G>T NP_001394792.1:p.Ser1470Ile missense NM_001407874.1:c.4328G>T NP_001394803.1:p.Ser1443Ile missense NM_001407875.1:c.4328G>T NP_001394804.1:p.Ser1443Ile missense NM_001407879.1:c.4325G>T NP_001394808.1:p.Ser1442Ile missense NM_001407881.1:c.4325G>T NP_001394810.1:p.Ser1442Ile missense NM_001407882.1:c.4325G>T NP_001394811.1:p.Ser1442Ile missense NM_001407884.1:c.4325G>T NP_001394813.1:p.Ser1442Ile missense NM_001407885.1:c.4325G>T NP_001394814.1:p.Ser1442Ile missense NM_001407886.1:c.4325G>T NP_001394815.1:p.Ser1442Ile missense NM_001407887.1:c.4325G>T NP_001394816.1:p.Ser1442Ile missense NM_001407889.1:c.4325G>T NP_001394818.1:p.Ser1442Ile missense NM_001407894.1:c.4322G>T NP_001394823.1:p.Ser1441Ile missense NM_001407895.1:c.4322G>T NP_001394824.1:p.Ser1441Ile missense NM_001407896.1:c.4322G>T NP_001394825.1:p.Ser1441Ile missense NM_001407897.1:c.4322G>T NP_001394826.1:p.Ser1441Ile missense NM_001407898.1:c.4322G>T NP_001394827.1:p.Ser1441Ile missense NM_001407899.1:c.4322G>T NP_001394828.1:p.Ser1441Ile missense NM_001407900.1:c.4322G>T NP_001394829.1:p.Ser1441Ile missense NM_001407902.1:c.4322G>T NP_001394831.1:p.Ser1441Ile missense NM_001407904.1:c.4322G>T NP_001394833.1:p.Ser1441Ile missense NM_001407906.1:c.4322G>T NP_001394835.1:p.Ser1441Ile missense NM_001407907.1:c.4322G>T NP_001394836.1:p.Ser1441Ile missense NM_001407908.1:c.4322G>T NP_001394837.1:p.Ser1441Ile missense NM_001407909.1:c.4322G>T NP_001394838.1:p.Ser1441Ile missense NM_001407910.1:c.4322G>T NP_001394839.1:p.Ser1441Ile missense NM_001407915.1:c.4319G>T NP_001394844.1:p.Ser1440Ile missense NM_001407916.1:c.4319G>T NP_001394845.1:p.Ser1440Ile missense NM_001407917.1:c.4319G>T NP_001394846.1:p.Ser1440Ile missense NM_001407918.1:c.4319G>T NP_001394847.1:p.Ser1440Ile missense NM_001407919.1:c.4412G>T NP_001394848.1:p.Ser1471Ile missense NM_001407920.1:c.4271G>T NP_001394849.1:p.Ser1424Ile missense NM_001407921.1:c.4271G>T NP_001394850.1:p.Ser1424Ile missense NM_001407922.1:c.4271G>T NP_001394851.1:p.Ser1424Ile missense NM_001407923.1:c.4271G>T NP_001394852.1:p.Ser1424Ile missense NM_001407924.1:c.4271G>T NP_001394853.1:p.Ser1424Ile missense NM_001407925.1:c.4271G>T NP_001394854.1:p.Ser1424Ile missense NM_001407926.1:c.4271G>T NP_001394855.1:p.Ser1424Ile missense NM_001407927.1:c.4268G>T NP_001394856.1:p.Ser1423Ile missense NM_001407928.1:c.4268G>T NP_001394857.1:p.Ser1423Ile missense NM_001407929.1:c.4268G>T NP_001394858.1:p.Ser1423Ile missense NM_001407930.1:c.4268G>T NP_001394859.1:p.Ser1423Ile missense NM_001407931.1:c.4268G>T NP_001394860.1:p.Ser1423Ile missense NM_001407932.1:c.4268G>T NP_001394861.1:p.Ser1423Ile missense NM_001407933.1:c.4268G>T NP_001394862.1:p.Ser1423Ile missense NM_001407934.1:c.4265G>T NP_001394863.1:p.Ser1422Ile missense NM_001407935.1:c.4265G>T NP_001394864.1:p.Ser1422Ile missense NM_001407936.1:c.4265G>T NP_001394865.1:p.Ser1422Ile missense NM_001407937.1:c.4412G>T NP_001394866.1:p.Ser1471Ile missense NM_001407938.1:c.4412G>T NP_001394867.1:p.Ser1471Ile missense NM_001407939.1:c.4409G>T NP_001394868.1:p.Ser1470Ile missense NM_001407940.1:c.4409G>T NP_001394869.1:p.Ser1470Ile missense NM_001407941.1:c.4406G>T NP_001394870.1:p.Ser1469Ile missense NM_001407942.1:c.4394G>T NP_001394871.1:p.Ser1465Ile missense NM_001407943.1:c.4391G>T NP_001394872.1:p.Ser1464Ile missense NM_001407944.1:c.4391G>T NP_001394873.1:p.Ser1464Ile missense NM_001407945.1:c.4391G>T NP_001394874.1:p.Ser1464Ile missense NM_001407946.1:c.4202G>T NP_001394875.1:p.Ser1401Ile missense NM_001407947.1:c.4202G>T NP_001394876.1:p.Ser1401Ile missense NM_001407948.1:c.4202G>T NP_001394877.1:p.Ser1401Ile missense NM_001407949.1:c.4202G>T NP_001394878.1:p.Ser1401Ile missense NM_001407950.1:c.4199G>T NP_001394879.1:p.Ser1400Ile missense NM_001407951.1:c.4199G>T NP_001394880.1:p.Ser1400Ile missense NM_001407952.1:c.4199G>T NP_001394881.1:p.Ser1400Ile missense NM_001407953.1:c.4199G>T NP_001394882.1:p.Ser1400Ile missense NM_001407954.1:c.4199G>T NP_001394883.1:p.Ser1400Ile missense NM_001407955.1:c.4199G>T NP_001394884.1:p.Ser1400Ile missense NM_001407956.1:c.4196G>T NP_001394885.1:p.Ser1399Ile missense NM_001407957.1:c.4196G>T NP_001394886.1:p.Ser1399Ile missense NM_001407958.1:c.4196G>T NP_001394887.1:p.Ser1399Ile missense NM_001407959.1:c.4154G>T NP_001394888.1:p.Ser1385Ile missense NM_001407960.1:c.4151G>T NP_001394889.1:p.Ser1384Ile missense NM_001407962.1:c.4151G>T NP_001394891.1:p.Ser1384Ile missense NM_001407963.1:c.4148G>T NP_001394892.1:p.Ser1383Ile missense NM_001407965.1:c.4028G>T NP_001394894.1:p.Ser1343Ile missense NM_001407966.1:c.3647G>T NP_001394895.1:p.Ser1216Ile missense NM_001407967.1:c.3644G>T NP_001394896.1:p.Ser1215Ile missense NM_001407968.1:c.1931G>T NP_001394897.1:p.Ser644Ile missense NM_001407969.1:c.1928G>T NP_001394898.1:p.Ser643Ile missense NM_001407970.1:c.1292G>T NP_001394899.1:p.Ser431Ile missense NM_001407971.1:c.1292G>T NP_001394900.1:p.Ser431Ile missense NM_001407972.1:c.1289G>T NP_001394901.1:p.Ser430Ile missense NM_001407973.1:c.1226G>T NP_001394902.1:p.Ser409Ile missense NM_001407974.1:c.1226G>T NP_001394903.1:p.Ser409Ile missense NM_001407975.1:c.1226G>T NP_001394904.1:p.Ser409Ile missense NM_001407976.1:c.1226G>T NP_001394905.1:p.Ser409Ile missense NM_001407977.1:c.1226G>T NP_001394906.1:p.Ser409Ile missense NM_001407978.1:c.1226G>T NP_001394907.1:p.Ser409Ile missense NM_001407979.1:c.1223G>T NP_001394908.1:p.Ser408Ile missense NM_001407980.1:c.1223G>T NP_001394909.1:p.Ser408Ile missense NM_001407981.1:c.1223G>T NP_001394910.1:p.Ser408Ile missense NM_001407982.1:c.1223G>T NP_001394911.1:p.Ser408Ile missense NM_001407983.1:c.1223G>T NP_001394912.1:p.Ser408Ile missense NM_001407984.1:c.1223G>T NP_001394913.1:p.Ser408Ile missense NM_001407985.1:c.1223G>T NP_001394914.1:p.Ser408Ile missense NM_001407986.1:c.1223G>T NP_001394915.1:p.Ser408Ile missense NM_001407990.1:c.1223G>T NP_001394919.1:p.Ser408Ile missense NM_001407991.1:c.1223G>T NP_001394920.1:p.Ser408Ile missense NM_001407992.1:c.1223G>T NP_001394921.1:p.Ser408Ile missense NM_001407993.1:c.1223G>T NP_001394922.1:p.Ser408Ile missense NM_001408392.1:c.1220G>T NP_001395321.1:p.Ser407Ile missense NM_001408396.1:c.1220G>T NP_001395325.1:p.Ser407Ile missense NM_001408397.1:c.1220G>T NP_001395326.1:p.Ser407Ile missense NM_001408398.1:c.1220G>T NP_001395327.1:p.Ser407Ile missense NM_001408399.1:c.1220G>T NP_001395328.1:p.Ser407Ile missense NM_001408400.1:c.1220G>T NP_001395329.1:p.Ser407Ile missense NM_001408401.1:c.1220G>T NP_001395330.1:p.Ser407Ile missense NM_001408402.1:c.1220G>T NP_001395331.1:p.Ser407Ile missense NM_001408403.1:c.1220G>T NP_001395332.1:p.Ser407Ile missense NM_001408404.1:c.1220G>T NP_001395333.1:p.Ser407Ile missense NM_001408406.1:c.1217G>T NP_001395335.1:p.Ser406Ile missense NM_001408407.1:c.1217G>T NP_001395336.1:p.Ser406Ile missense NM_001408408.1:c.1217G>T NP_001395337.1:p.Ser406Ile missense NM_001408409.1:c.1214G>T NP_001395338.1:p.Ser405Ile missense NM_001408410.1:c.1151G>T NP_001395339.1:p.Ser384Ile missense NM_001408411.1:c.1148G>T NP_001395340.1:p.Ser383Ile missense NM_001408412.1:c.1145G>T NP_001395341.1:p.Ser382Ile missense NM_001408413.1:c.1145G>T NP_001395342.1:p.Ser382Ile missense NM_001408414.1:c.1145G>T NP_001395343.1:p.Ser382Ile missense NM_001408415.1:c.1145G>T NP_001395344.1:p.Ser382Ile missense NM_001408416.1:c.1145G>T NP_001395345.1:p.Ser382Ile missense NM_001408418.1:c.1109G>T NP_001395347.1:p.Ser370Ile missense NM_001408419.1:c.1109G>T NP_001395348.1:p.Ser370Ile missense NM_001408420.1:c.1109G>T NP_001395349.1:p.Ser370Ile missense NM_001408421.1:c.1106G>T NP_001395350.1:p.Ser369Ile missense NM_001408422.1:c.1106G>T NP_001395351.1:p.Ser369Ile missense NM_001408423.1:c.1106G>T NP_001395352.1:p.Ser369Ile missense NM_001408424.1:c.1106G>T NP_001395353.1:p.Ser369Ile missense NM_001408425.1:c.1103G>T NP_001395354.1:p.Ser368Ile missense NM_001408426.1:c.1103G>T NP_001395355.1:p.Ser368Ile missense NM_001408427.1:c.1103G>T NP_001395356.1:p.Ser368Ile missense NM_001408428.1:c.1103G>T NP_001395357.1:p.Ser368Ile missense NM_001408429.1:c.1103G>T NP_001395358.1:p.Ser368Ile missense NM_001408430.1:c.1103G>T NP_001395359.1:p.Ser368Ile missense NM_001408431.1:c.1103G>T NP_001395360.1:p.Ser368Ile missense NM_001408432.1:c.1100G>T NP_001395361.1:p.Ser367Ile missense NM_001408433.1:c.1100G>T NP_001395362.1:p.Ser367Ile missense NM_001408434.1:c.1100G>T NP_001395363.1:p.Ser367Ile missense NM_001408435.1:c.1100G>T NP_001395364.1:p.Ser367Ile missense NM_001408436.1:c.1100G>T NP_001395365.1:p.Ser367Ile missense NM_001408437.1:c.1100G>T NP_001395366.1:p.Ser367Ile missense NM_001408438.1:c.1100G>T NP_001395367.1:p.Ser367Ile missense NM_001408439.1:c.1100G>T NP_001395368.1:p.Ser367Ile missense NM_001408440.1:c.1100G>T NP_001395369.1:p.Ser367Ile missense NM_001408441.1:c.1100G>T NP_001395370.1:p.Ser367Ile missense NM_001408442.1:c.1100G>T NP_001395371.1:p.Ser367Ile missense NM_001408443.1:c.1100G>T NP_001395372.1:p.Ser367Ile missense NM_001408444.1:c.1100G>T NP_001395373.1:p.Ser367Ile missense NM_001408445.1:c.1097G>T NP_001395374.1:p.Ser366Ile missense NM_001408446.1:c.1097G>T NP_001395375.1:p.Ser366Ile missense NM_001408447.1:c.1097G>T NP_001395376.1:p.Ser366Ile missense NM_001408448.1:c.1097G>T NP_001395377.1:p.Ser366Ile missense NM_001408450.1:c.1097G>T NP_001395379.1:p.Ser366Ile missense NM_001408451.1:c.1091G>T NP_001395380.1:p.Ser364Ile missense NM_001408452.1:c.1085G>T NP_001395381.1:p.Ser362Ile missense NM_001408453.1:c.1085G>T NP_001395382.1:p.Ser362Ile missense NM_001408454.1:c.1085G>T NP_001395383.1:p.Ser362Ile missense NM_001408455.1:c.1085G>T NP_001395384.1:p.Ser362Ile missense NM_001408456.1:c.1085G>T NP_001395385.1:p.Ser362Ile missense NM_001408457.1:c.1085G>T NP_001395386.1:p.Ser362Ile missense NM_001408458.1:c.1082G>T NP_001395387.1:p.Ser361Ile missense NM_001408459.1:c.1082G>T NP_001395388.1:p.Ser361Ile missense NM_001408460.1:c.1082G>T NP_001395389.1:p.Ser361Ile missense NM_001408461.1:c.1082G>T NP_001395390.1:p.Ser361Ile missense NM_001408462.1:c.1082G>T NP_001395391.1:p.Ser361Ile missense NM_001408463.1:c.1082G>T NP_001395392.1:p.Ser361Ile missense NM_001408464.1:c.1082G>T NP_001395393.1:p.Ser361Ile missense NM_001408465.1:c.1082G>T NP_001395394.1:p.Ser361Ile missense NM_001408466.1:c.1082G>T NP_001395395.1:p.Ser361Ile missense NM_001408467.1:c.1082G>T NP_001395396.1:p.Ser361Ile missense NM_001408468.1:c.1079G>T NP_001395397.1:p.Ser360Ile missense NM_001408469.1:c.1079G>T NP_001395398.1:p.Ser360Ile missense NM_001408470.1:c.1079G>T NP_001395399.1:p.Ser360Ile missense NM_001408472.1:c.1223G>T NP_001395401.1:p.Ser408Ile missense NM_001408473.1:c.1220G>T NP_001395402.1:p.Ser407Ile missense NM_001408474.1:c.1025G>T NP_001395403.1:p.Ser342Ile missense NM_001408475.1:c.1022G>T NP_001395404.1:p.Ser341Ile missense NM_001408476.1:c.1022G>T NP_001395405.1:p.Ser341Ile missense NM_001408478.1:c.1016G>T NP_001395407.1:p.Ser339Ile missense NM_001408479.1:c.1016G>T NP_001395408.1:p.Ser339Ile missense NM_001408480.1:c.1016G>T NP_001395409.1:p.Ser339Ile missense NM_001408481.1:c.1013G>T NP_001395410.1:p.Ser338Ile missense NM_001408482.1:c.1013G>T NP_001395411.1:p.Ser338Ile missense NM_001408483.1:c.1013G>T NP_001395412.1:p.Ser338Ile missense NM_001408484.1:c.1013G>T NP_001395413.1:p.Ser338Ile missense NM_001408485.1:c.1013G>T NP_001395414.1:p.Ser338Ile missense NM_001408489.1:c.1013G>T NP_001395418.1:p.Ser338Ile missense NM_001408490.1:c.1013G>T NP_001395419.1:p.Ser338Ile missense NM_001408491.1:c.1013G>T NP_001395420.1:p.Ser338Ile missense NM_001408492.1:c.1010G>T NP_001395421.1:p.Ser337Ile missense NM_001408493.1:c.1010G>T NP_001395422.1:p.Ser337Ile missense NM_001408494.1:c.986G>T NP_001395423.1:p.Ser329Ile missense NM_001408495.1:c.980G>T NP_001395424.1:p.Ser327Ile missense NM_001408496.1:c.962G>T NP_001395425.1:p.Ser321Ile missense NM_001408497.1:c.962G>T NP_001395426.1:p.Ser321Ile missense NM_001408498.1:c.962G>T NP_001395427.1:p.Ser321Ile missense NM_001408499.1:c.962G>T NP_001395428.1:p.Ser321Ile missense NM_001408500.1:c.962G>T NP_001395429.1:p.Ser321Ile missense NM_001408501.1:c.962G>T NP_001395430.1:p.Ser321Ile missense NM_001408502.1:c.959G>T NP_001395431.1:p.Ser320Ile missense NM_001408503.1:c.959G>T NP_001395432.1:p.Ser320Ile missense NM_001408504.1:c.959G>T NP_001395433.1:p.Ser320Ile missense NM_001408505.1:c.956G>T NP_001395434.1:p.Ser319Ile missense NM_001408506.1:c.899G>T NP_001395435.1:p.Ser300Ile missense NM_001408507.1:c.896G>T NP_001395436.1:p.Ser299Ile missense NM_001408508.1:c.887G>T NP_001395437.1:p.Ser296Ile missense NM_001408509.1:c.884G>T NP_001395438.1:p.Ser295Ile missense NM_001408510.1:c.845G>T NP_001395439.1:p.Ser282Ile missense NM_001408511.1:c.842G>T NP_001395440.1:p.Ser281Ile missense NM_001408512.1:c.722G>T NP_001395441.1:p.Ser241Ile missense NM_007297.4:c.4394G>T NP_009228.2:p.Ser1465Ile missense NM_007298.4:c.1223G>T NP_009229.2:p.Ser408Ile missense NM_007299.4:c.1223G>T NP_009230.2:p.Ser408Ile missense NM_007300.4:c.4598G>T NP_009231.2:p.Ser1533Ile missense NM_007304.2:c.1223G>T NP_009235.2:p.Ser408Ile missense NR_027676.2:n.4712G>T non-coding transcript variant NC_000017.11:g.43074471C>A NC_000017.10:g.41226488C>A NG_005905.2:g.143513G>T LRG_292:g.143513G>T LRG_292t1:c.4535G>T LRG_292p1:p.Ser1512Ile P38398:p.Ser1512Ile U14680.1:n.4654G>T - Protein change
- S1512I, S408I, S1533I, S1465I, S1343I, S1385I, S1441I, S1442I, S1468I, S1492I, S1508I, S1509I, S1510I, S296I, S321I, S361I, S366I, S370I, S383I, S409I, S644I, S1215I, S1422I, S1423I, S1440I, S1445I, S1463I, S1464I, S1471I, S1493I, S1507I, S241I, S282I, S327I, S329I, S337I, S341I, S342I, S362I, S367I, S384I, S407I, S430I, S1383I, S1400I, S1401I, S1443I, S1469I, S1484I, S1485I, S1486I, S1511I, S1534I, S281I, S299I, S338I, S364I, S369I, S382I, S405I, S406I, S431I, S1216I, S1384I, S1399I, S1424I, S1470I, S1532I, S295I, S300I, S319I, S320I, S339I, S360I, S368I, S643I
- Other names
-
NP_009225.1:p.Ser1512Ile
4654G>T
- Canonical SPDI
- NC_000017.11:43074470:C:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00060 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 0.00060
1000 Genomes Project 30x 0.00078
Exome Aggregation Consortium (ExAC) 0.00215
The Genome Aggregation Database (gnomAD), exomes 0.00237
The Genome Aggregation Database (gnomAD) 0.00240
Trans-Omics for Precision Medicine (TOPMed) 0.00241
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00277
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13050 | 14856 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Aug 1, 2024 | RCV000034752.44 | |
| Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000048591.30 | |
| Benign (13) |
reviewed by expert panel
|
Aug 10, 2015 | RCV000112356.28 | |
| Benign (12) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2023 | RCV000120258.38 | |
| Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
May 20, 2020 | RCV000162492.16 | |
| Benign (1) |
criteria provided, single submitter
|
Dec 23, 2021 | RCV002490467.8 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Benign
(Aug 10, 2015)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000244362.1
First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015 |
Comment:
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on … (more)
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000000000309 (less)
|
|
|
Benign
(Dec 09, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000593659.1
First in ClinVar: Aug 27, 2017 Last updated: Aug 27, 2017 |
|
|
|
Benign
(Nov 07, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000806953.1
First in ClinVar: Dec 02, 2017 Last updated: Dec 02, 2017 |
|
|
|
Likely benign
(Aug 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002498278.18
First in ClinVar: Apr 11, 2022 Last updated: Oct 20, 2024 |
Comment:
BRCA1: BS2
Number of individuals with the variant: 23
|
|
|
Benign
(Jul 10, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000226128.5
First in ClinVar: Jun 28, 2015 Last updated: Sep 22, 2018 |
Number of individuals with the variant: 4
Sex: mixed
|
|
|
Benign
(Jun 15, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001469392.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021 |
|
|
|
Benign
(May 20, 2020)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002537758.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
|
|
Benign
(Jul 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004016787.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
|
|
|
Benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002550974.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
|
|
|
Benign
(Nov 03, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000195930.1
First in ClinVar: May 06, 2016 Last updated: May 06, 2016 |
Tissue: Blood
|
|
|
Benign
(Apr 18, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000586900.1 First in ClinVar: Oct 22, 2016 Last updated: Oct 22, 2016 |
|
|
|
Benign
(Oct 09, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743392.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Benign
(Sep 21, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744613.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Likely benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001140518.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
|
|
|
Benign
(Aug 07, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001280758.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
|
|
|
Benign
(Apr 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002025932.2
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 3
Geographic origin: South Africa
|
|
|
Likely benign
(Nov 01, 2021)
|
criteria provided, single submitter
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Genetics Program, Instituto Nacional de Cancer
Accession: SCV002515214.1
First in ClinVar: Nov 19, 2022 Last updated: Nov 19, 2022 |
Geographic origin: Brazil
|
|
|
Benign
(Jan 24, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000494296.2
First in ClinVar: Feb 04, 2017 Last updated: Dec 11, 2022 |
|
|
|
Likely benign
(Nov 11, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683192.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
|
|
|
Benign
(Mar 19, 2014)
|
criteria provided, single submitter
Method: literature only
|
Breast-ovarian cancer, familial 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000154028.2
First in ClinVar: Jun 04, 2014 Last updated: Dec 24, 2022 |
|
|
|
Benign
(Dec 23, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Breast-ovarian cancer, familial, susceptibility to, 1 Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002803547.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000076604.14
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
|
|
|
Benign
(Sep 25, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602672.8
First in ClinVar: Aug 27, 2017 Last updated: Feb 20, 2024 |
|
|
|
Likely Benign
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004817658.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Number of individuals with the variant: 684
|
|
|
Benign
(Jul 21, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000212874.6
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005251036.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
no known pathogenicity
(Jul 13, 2012)
|
no assertion criteria provided
Method: research
|
not provided
Affected status: no
Allele origin:
germline
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043157.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Benign.
Number of individuals with the variant: 6
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
|
|
|
Benign
(Mar 08, 2011)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000189343.1
First in ClinVar: Sep 27, 2014 Last updated: Sep 27, 2014 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733609.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Likely benign
(Jul 24, 2014)
|
no assertion criteria provided
Method: literature only
|
hereditary breast and ovarian cancer, BROVCA1
Affected status: unknown
Allele origin:
germline
|
Pathway Genomics
Accession: SCV000187728.1
First in ClinVar: Aug 15, 2014 Last updated: Aug 15, 2014 |
|
|
|
Benign
(Jun 21, 1999)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline,
unknown
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145117.2
First in ClinVar: Apr 01, 2014 Last updated: Sep 29, 2015 |
Observation 1:
Number of individuals with the variant: 34
Observation 2:
Number of individuals with the variant: 1
Geographic origin: American
Observation 3:
Number of individuals with the variant: 4
Geographic origin: Austria
Observation 4:
Number of individuals with the variant: 4
Geographic origin: Netherlands
Observation 5:
Number of individuals with the variant: 1
Geographic origin: Italy
Observation 6:
Number of individuals with the variant: 3
Geographic origin: Western European
Observation 7:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: American
Observation 8:
Number of individuals with the variant: 3
Ethnicity/Population group: Caucasian
Geographic origin: Denmark
Observation 9:
Number of individuals with the variant: 3
Ethnicity/Population group: Caucasian
Geographic origin: Germany
Observation 10:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Germany, France
Observation 11:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Spain
Observation 12:
Number of individuals with the variant: 1
Ethnicity/Population group: Celtic
Geographic origin: France
Observation 13:
Number of individuals with the variant: 1
Ethnicity/Population group: European
Geographic origin: Germany
Observation 14:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European
Observation 15:
Number of individuals with the variant: 1
Geographic origin: France
|
|
|
Benign
(Jan 31, 2014)
|
no assertion criteria provided
Method: research
|
not specified
Affected status: yes
Allele origin:
germline
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587407.1 First in ClinVar: Oct 22, 2016 Last updated: Oct 22, 2016 |
|
|
|
Benign
(Dec 06, 2016)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000778738.1
First in ClinVar: Feb 24, 2015 Last updated: Feb 24, 2015 |
|
|
|
Likely benign
(Apr 25, 2018)
|
no assertion criteria provided
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
True Health Diagnostics
Accession: SCV000805231.1
First in ClinVar: May 03, 2018 Last updated: May 03, 2018 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591526.2 First in ClinVar: Aug 27, 2017 Last updated: Jan 26, 2021 |
Comment:
The BRCA1, c.4535G>T, p.Ser1512Ile variant has been reported in the literature in 6/2156 proband chromosomes of individuals with HBOC and sporadic breast/ ovarian cancer. It … (more)
The BRCA1, c.4535G>T, p.Ser1512Ile variant has been reported in the literature in 6/2156 proband chromosomes of individuals with HBOC and sporadic breast/ ovarian cancer. It was also identified in 6/1360 of the control chromosomes evaluated (Al-Mulla_2008, Bergthorsson_2001, Young_2009, Wagner_1998, Tavtigian_2006, Phelan_2005, Sanz_2010). The variant has also been previously identified in our laboratory in 6 individuals, and was classified as benign. The variant is reported in the BIC (x58), Exome Server and BOCs databases. It is also listed in the dbSNP database as coming from a "clinical source" (ID#: rs1800744) with a MAF score of 0.001 (1000 Genomes), increasing the likelihood that this is a low frequency benign variant. The residue is not conserved in mammals, and computational analyses (PolyPhen, SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein. However, this information is not very predictive of pathogenicity. Functional studies examining the effect of the variant on transcriptional activation found that the variant levels were equal to or higher than that of wild type BRCA1, suggesting that it does not represent a high risk variant & is likely to have low clinical significance (Phelan_2005). Studies have also reported that p.Ser1512Ile has been found to co-occur with other known BRCA1 pathogenic variants numerous times, increasing the likelihood that this variant does not have clinical significance (Bergthorsson_2001, Tavtigian_2006, Phelan_2005). In summary, based on the above information, this variant is classified as Benign. (less)
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001906427.1 First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953385.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
|
Benign
(Sep 27, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV001977041.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002035335.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
|
|
|
not provided
(Sep 19, 2013)
|
no classification provided
Method: reference population
|
AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
|
ITMI
Accession: SCV000084410.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
|
Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
|
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Comment:
Comment:
BRCA1: BS2
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
Converted during submission to Benign.
Comment:
The BRCA1, c.4535G>T, p.Ser1512Ile variant has been reported in the literature in 6/2156 proband chromosomes of individuals with HBOC and sporadic breast/ ovarian cancer. It was also identified in 6/1360 of the control chromosomes evaluated (Al-Mulla_2008, Bergthorsson_2001, Young_2009, Wagner_1998, Tavtigian_2006, Phelan_2005, Sanz_2010). The variant has also been previously identified in our laboratory in 6 individuals, and was classified as benign. The variant is reported in the BIC (x58), Exome Server and BOCs databases. It is also listed in the dbSNP database as coming from a "clinical source" (ID#: rs1800744) with a MAF score of 0.001 (1000 Genomes), increasing the likelihood that this is a low frequency benign variant. The residue is not conserved in mammals, and computational analyses (PolyPhen, SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein. However, this information is not very predictive of pathogenicity. Functional studies examining the effect of the variant on transcriptional activation found that the variant levels were equal to or higher than that of wild type BRCA1, suggesting that it does not represent a high risk variant & is likely to have low clinical significance (Phelan_2005). Studies have also reported that p.Ser1512Ile has been found to co-occur with other known BRCA1 pathogenic variants numerous times, increasing the likelihood that this variant does not have clinical significance (Bergthorsson_2001, Tavtigian_2006, Phelan_2005). In summary, based on the above information, this variant is classified as Benign.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000000000309
Comment:
BRCA1: BS2
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
Converted during submission to Benign.
Comment:
The BRCA1, c.4535G>T, p.Ser1512Ile variant has been reported in the literature in 6/2156 proband chromosomes of individuals with HBOC and sporadic breast/ ovarian cancer. It was also identified in 6/1360 of the control chromosomes evaluated (Al-Mulla_2008, Bergthorsson_2001, Young_2009, Wagner_1998, Tavtigian_2006, Phelan_2005, Sanz_2010). The variant has also been previously identified in our laboratory in 6 individuals, and was classified as benign. The variant is reported in the BIC (x58), Exome Server and BOCs databases. It is also listed in the dbSNP database as coming from a "clinical source" (ID#: rs1800744) with a MAF score of 0.001 (1000 Genomes), increasing the likelihood that this is a low frequency benign variant. The residue is not conserved in mammals, and computational analyses (PolyPhen, SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein. However, this information is not very predictive of pathogenicity. Functional studies examining the effect of the variant on transcriptional activation found that the variant levels were equal to or higher than that of wild type BRCA1, suggesting that it does not represent a high risk variant & is likely to have low clinical significance (Phelan_2005). Studies have also reported that p.Ser1512Ile has been found to co-occur with other known BRCA1 pathogenic variants numerous times, increasing the likelihood that this variant does not have clinical significance (Bergthorsson_2001, Tavtigian_2006, Phelan_2005). In summary, based on the above information, this variant is classified as Benign.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service. | Matta BP | Scientific reports | 2022 | PMID: 36329109 |
| Prevalence of Clinically Relevant Germline BRCA Variants in a Large Unselected South African Breast and Ovarian Cancer Cohort: A Public Sector Experience. | Van der Merwe NC | Frontiers in genetics | 2022 | DOI: 10.3389/fgene.2022.834265 |
| Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. | Johnston JJ | American journal of human genetics | 2012 | PMID: 22703879 |
| A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS). | Lindor NM | Human mutation | 2012 | PMID: 21990134 |
| A high-throughput protocol for mutation scanning of the BRCA1 and BRCA2 genes. | Hondow HL | BMC cancer | 2011 | PMID: 21702907 |
| Assessment of rare BRCA1 and BRCA2 variants of unknown significance using hierarchical modeling. | Capanu M | Genetic epidemiology | 2011 | PMID: 21520273 |
| A computational method to classify variants of uncertain significance using functional assay data with application to BRCA1. | Iversen ES Jr | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2011 | PMID: 21447777 |
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
| A yeast recombination assay to characterize human BRCA1 missense variants of unknown pathological significance. | Caligo MA | Human mutation | 2009 | PMID: 18680205 |
| Determination of cancer risk associated with germ line BRCA1 missense variants by functional analysis. | Carvalho MA | Cancer research | 2007 | PMID: 17308087 |
| Classification of missense variants of unknown significance in BRCA1 based on clinical and tumor information. | Osorio A | Human mutation | 2007 | PMID: 17279547 |
| Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral. | Tavtigian SV | Journal of medical genetics | 2006 | PMID: 16014699 |
| Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. | Judkins T | Cancer research | 2005 | PMID: 16267036 |
| Classification of BRCA1 missense variants of unknown clinical significance. | Phelan CM | Journal of medical genetics | 2005 | PMID: 15689452 |
| Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation. | Abkevich V | Journal of medical genetics | 2004 | PMID: 15235020 |
| Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects. | Díez O | Human mutation | 2003 | PMID: 12955716 |
| Prevalence of BRCA1 and BRCA2 germline mutations in young breast cancer patients: a population-based study. | de Sanjosé S | International journal of cancer | 2003 | PMID: 12845657 |
| A low frequency of non-founder BRCA1 mutations in Ashkenazi Jewish breast-ovarian cancer families. | Phelan CM | Human mutation | 2002 | PMID: 12402332 |
| Characterization of common BRCA1 and BRCA2 variants. | Deffenbaugh AM | Genetic testing | 2002 | PMID: 12215251 |
| Loss of heterozygosity analysis at the BRCA loci in tumor samples from patients with familial breast cancer. | Osorio A | International journal of cancer | 2002 | PMID: 11979449 |
| BRCA1 and BRCA2 mutation status and cancer family history of Danish women affected with multifocal or bilateral breast cancer at a young age. | Bergthorsson JT | Journal of medical genetics | 2001 | PMID: 11389159 |
| Spanish family study on hereditary breast and/or ovarian cancer: analysis of the BRCA1 gene. | de la Hoya M | International journal of cancer | 2001 | PMID: 11149413 |
| Identification of missense and truncating mutations in the BRCA1 gene in sporadic and familial breast and ovarian cancer. | Greenman J | Genes, chromosomes & cancer | 1998 | PMID: 9523200 |
| Low frequency of BRCA1 germline mutations in 45 German breast/ovarian cancer families. | Hamann U | Journal of medical genetics | 1997 | PMID: 9391879 |
| BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family cancer clinic. Institut Curie Breast Cancer Group. | Stoppa-Lyonnet D | American journal of human genetics | 1997 | PMID: 9150149 |
| Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene. Breast Cancer Information Core. | Couch FJ | Human mutation | 1996 | PMID: 8807330 |
| http://hci-exlovd.hci.utah.edu/variants.php?select_db=BRCA1&action=search_all&search_Variant%2FDNA=c.4535G%3ET | - | - | - | - |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA1 | - | - | - | - |
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Text-mined citations for rs1800744 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.