VCV000224562.25 - ClinVar

NM_007294.4(BRCA1):c.301+6T>C

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(13)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Likely pathogenic(1); Uncertain significance(10)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_007294.4(BRCA1):c.301+6T>C

Variation ID: 224562 Accession: VCV000224562.25

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.31 17: 43104862 (GRCh38) [ NCBI UCSC ] 17: 41256879 (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	Mar 20, 2016	Nov 24, 2024	Apr 12, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_007294.4:c.301+6T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001407571.1:c.91+6T>C		intron variant
NM_001407581.1:c.301+6T>C		intron variant
NM_001407582.1:c.301+6T>C		intron variant
NM_001407583.1:c.301+6T>C		intron variant
NM_001407585.1:c.301+6T>C		intron variant
NM_001407587.1:c.301+6T>C		intron variant
NM_001407590.1:c.301+6T>C		intron variant
NM_001407591.1:c.301+6T>C		intron variant
NM_001407593.1:c.301+6T>C		intron variant
NM_001407594.1:c.301+6T>C		intron variant
NM_001407596.1:c.301+6T>C		intron variant
NM_001407597.1:c.301+6T>C		intron variant
NM_001407598.1:c.301+6T>C		intron variant
NM_001407602.1:c.301+6T>C		intron variant
NM_001407603.1:c.301+6T>C		intron variant
NM_001407605.1:c.301+6T>C		intron variant
NM_001407610.1:c.301+6T>C		intron variant
NM_001407611.1:c.301+6T>C		intron variant
NM_001407612.1:c.301+6T>C		intron variant
NM_001407613.1:c.301+6T>C		intron variant
NM_001407614.1:c.301+6T>C		intron variant
NM_001407615.1:c.301+6T>C		intron variant
NM_001407616.1:c.301+6T>C		intron variant
NM_001407617.1:c.301+6T>C		intron variant
NM_001407618.1:c.301+6T>C		intron variant
NM_001407619.1:c.301+6T>C		intron variant
NM_001407620.1:c.301+6T>C		intron variant
NM_001407621.1:c.301+6T>C		intron variant
NM_001407622.1:c.301+6T>C		intron variant
NM_001407623.1:c.301+6T>C		intron variant
NM_001407624.1:c.301+6T>C		intron variant
NM_001407625.1:c.301+6T>C		intron variant
NM_001407626.1:c.301+6T>C		intron variant
NM_001407627.1:c.301+6T>C		intron variant
NM_001407628.1:c.301+6T>C		intron variant
NM_001407629.1:c.301+6T>C		intron variant
NM_001407630.1:c.301+6T>C		intron variant
NM_001407631.1:c.301+6T>C		intron variant
NM_001407632.1:c.301+6T>C		intron variant
NM_001407633.1:c.301+6T>C		intron variant
NM_001407634.1:c.301+6T>C		intron variant
NM_001407635.1:c.301+6T>C		intron variant
NM_001407636.1:c.301+6T>C		intron variant
NM_001407637.1:c.301+6T>C		intron variant
NM_001407638.1:c.301+6T>C		intron variant
NM_001407639.1:c.301+6T>C		intron variant
NM_001407640.1:c.301+6T>C		intron variant
NM_001407641.1:c.301+6T>C		intron variant
NM_001407642.1:c.301+6T>C		intron variant
NM_001407644.1:c.301+6T>C		intron variant
NM_001407645.1:c.301+6T>C		intron variant
NM_001407646.1:c.292+15T>C		intron variant
NM_001407647.1:c.292+15T>C		intron variant
NM_001407648.1:c.301+6T>C		intron variant
NM_001407649.1:c.301+6T>C		intron variant
NM_001407652.1:c.301+6T>C		intron variant
NM_001407653.1:c.223+6T>C		intron variant
NM_001407654.1:c.223+6T>C		intron variant
NM_001407655.1:c.223+6T>C		intron variant
NM_001407656.1:c.223+6T>C		intron variant
NM_001407657.1:c.223+6T>C		intron variant
NM_001407658.1:c.223+6T>C		intron variant
NM_001407659.1:c.223+6T>C		intron variant
NM_001407660.1:c.223+6T>C		intron variant
NM_001407661.1:c.223+6T>C		intron variant
NM_001407662.1:c.223+6T>C		intron variant
NM_001407663.1:c.223+6T>C		intron variant
NM_001407664.1:c.301+6T>C		intron variant
NM_001407665.1:c.301+6T>C		intron variant
NM_001407666.1:c.301+6T>C		intron variant
NM_001407667.1:c.301+6T>C		intron variant
NM_001407668.1:c.301+6T>C		intron variant
NM_001407669.1:c.301+6T>C		intron variant
NM_001407670.1:c.301+6T>C		intron variant
NM_001407671.1:c.301+6T>C		intron variant
NM_001407672.1:c.301+6T>C		intron variant
NM_001407673.1:c.301+6T>C		intron variant
NM_001407674.1:c.301+6T>C		intron variant
NM_001407675.1:c.301+6T>C		intron variant
NM_001407676.1:c.301+6T>C		intron variant
NM_001407677.1:c.301+6T>C		intron variant
NM_001407678.1:c.301+6T>C		intron variant
NM_001407679.1:c.301+6T>C		intron variant
NM_001407680.1:c.301+6T>C		intron variant
NM_001407681.1:c.301+6T>C		intron variant
NM_001407682.1:c.301+6T>C		intron variant
NM_001407683.1:c.301+6T>C		intron variant
NM_001407684.1:c.301+6T>C		intron variant
NM_001407685.1:c.301+6T>C		intron variant
NM_001407686.1:c.301+6T>C		intron variant
NM_001407687.1:c.301+6T>C		intron variant
NM_001407688.1:c.301+6T>C		intron variant
NM_001407689.1:c.301+6T>C		intron variant
NM_001407690.1:c.301+6T>C		intron variant
NM_001407691.1:c.301+6T>C		intron variant
NM_001407692.1:c.160+6T>C		intron variant
NM_001407694.1:c.160+6T>C		intron variant
NM_001407695.1:c.160+6T>C		intron variant
NM_001407696.1:c.160+6T>C		intron variant
NM_001407697.1:c.160+6T>C		intron variant
NM_001407698.1:c.160+6T>C		intron variant
NM_001407724.1:c.160+6T>C		intron variant
NM_001407725.1:c.160+6T>C		intron variant
NM_001407726.1:c.160+6T>C		intron variant
NM_001407727.1:c.160+6T>C		intron variant
NM_001407728.1:c.160+6T>C		intron variant
NM_001407729.1:c.160+6T>C		intron variant
NM_001407730.1:c.160+6T>C		intron variant
NM_001407731.1:c.160+6T>C		intron variant
NM_001407732.1:c.160+6T>C		intron variant
NM_001407733.1:c.160+6T>C		intron variant
NM_001407734.1:c.160+6T>C		intron variant
NM_001407735.1:c.160+6T>C		intron variant
NM_001407736.1:c.160+6T>C		intron variant
NM_001407737.1:c.160+6T>C		intron variant
NM_001407738.1:c.160+6T>C		intron variant
NM_001407739.1:c.160+6T>C		intron variant
NM_001407740.1:c.160+6T>C		intron variant
NM_001407741.1:c.160+6T>C		intron variant
NM_001407742.1:c.160+6T>C		intron variant
NM_001407743.1:c.160+6T>C		intron variant
NM_001407744.1:c.160+6T>C		intron variant
NM_001407745.1:c.160+6T>C		intron variant
NM_001407746.1:c.160+6T>C		intron variant
NM_001407747.1:c.160+6T>C		intron variant
NM_001407748.1:c.160+6T>C		intron variant
NM_001407749.1:c.160+6T>C		intron variant
NM_001407750.1:c.160+6T>C		intron variant
NM_001407751.1:c.160+6T>C		intron variant
NM_001407752.1:c.160+6T>C		intron variant
NM_001407838.1:c.160+6T>C		intron variant
NM_001407839.1:c.160+6T>C		intron variant
NM_001407841.1:c.160+6T>C		intron variant
NM_001407842.1:c.160+6T>C		intron variant
NM_001407843.1:c.160+6T>C		intron variant
NM_001407844.1:c.160+6T>C		intron variant
NM_001407845.1:c.160+6T>C		intron variant
NM_001407846.1:c.160+6T>C		intron variant
NM_001407847.1:c.160+6T>C		intron variant
NM_001407848.1:c.160+6T>C		intron variant
NM_001407849.1:c.160+6T>C		intron variant
NM_001407850.1:c.160+6T>C		intron variant
NM_001407851.1:c.160+6T>C		intron variant
NM_001407852.1:c.160+6T>C		intron variant
NM_001407853.1:c.91+6T>C		intron variant
NM_001407854.1:c.301+6T>C		intron variant
NM_001407858.1:c.301+6T>C		intron variant
NM_001407859.1:c.301+6T>C		intron variant
NM_001407860.1:c.301+6T>C		intron variant
NM_001407861.1:c.301+6T>C		intron variant
NM_001407862.1:c.223+6T>C		intron variant
NM_001407863.1:c.301+6T>C		intron variant
NM_001407874.1:c.223+6T>C		intron variant
NM_001407875.1:c.223+6T>C		intron variant
NM_001407879.1:c.91+6T>C		intron variant
NM_001407881.1:c.91+6T>C		intron variant
NM_001407882.1:c.91+6T>C		intron variant
NM_001407884.1:c.91+6T>C		intron variant
NM_001407885.1:c.91+6T>C		intron variant
NM_001407886.1:c.91+6T>C		intron variant
NM_001407887.1:c.91+6T>C		intron variant
NM_001407889.1:c.91+6T>C		intron variant
NM_001407894.1:c.91+6T>C		intron variant
NM_001407895.1:c.91+6T>C		intron variant
NM_001407896.1:c.91+6T>C		intron variant
NM_001407897.1:c.91+6T>C		intron variant
NM_001407898.1:c.91+6T>C		intron variant
NM_001407899.1:c.91+6T>C		intron variant
NM_001407900.1:c.91+6T>C		intron variant
NM_001407902.1:c.91+6T>C		intron variant
NM_001407904.1:c.91+6T>C		intron variant
NM_001407906.1:c.91+6T>C		intron variant
NM_001407907.1:c.91+6T>C		intron variant
NM_001407908.1:c.91+6T>C		intron variant
NM_001407909.1:c.91+6T>C		intron variant
NM_001407910.1:c.91+6T>C		intron variant
NM_001407915.1:c.91+6T>C		intron variant
NM_001407916.1:c.91+6T>C		intron variant
NM_001407917.1:c.91+6T>C		intron variant
NM_001407918.1:c.91+6T>C		intron variant
NM_001407919.1:c.301+6T>C		intron variant
NM_001407920.1:c.160+6T>C		intron variant
NM_001407921.1:c.160+6T>C		intron variant
NM_001407922.1:c.160+6T>C		intron variant
NM_001407923.1:c.160+6T>C		intron variant
NM_001407924.1:c.160+6T>C		intron variant
NM_001407925.1:c.160+6T>C		intron variant
NM_001407926.1:c.160+6T>C		intron variant
NM_001407927.1:c.160+6T>C		intron variant
NM_001407928.1:c.160+6T>C		intron variant
NM_001407929.1:c.160+6T>C		intron variant
NM_001407930.1:c.160+6T>C		intron variant
NM_001407931.1:c.160+6T>C		intron variant
NM_001407932.1:c.160+6T>C		intron variant
NM_001407933.1:c.160+6T>C		intron variant
NM_001407934.1:c.160+6T>C		intron variant
NM_001407935.1:c.160+6T>C		intron variant
NM_001407936.1:c.160+6T>C		intron variant
NM_001407937.1:c.301+6T>C		intron variant
NM_001407938.1:c.301+6T>C		intron variant
NM_001407939.1:c.301+6T>C		intron variant
NM_001407940.1:c.301+6T>C		intron variant
NM_001407941.1:c.301+6T>C		intron variant
NM_001407942.1:c.160+6T>C		intron variant
NM_001407943.1:c.160+6T>C		intron variant
NM_001407944.1:c.160+6T>C		intron variant
NM_001407945.1:c.160+6T>C		intron variant
NM_001407946.1:c.91+6T>C		intron variant
NM_001407947.1:c.91+6T>C		intron variant
NM_001407948.1:c.91+6T>C		intron variant
NM_001407949.1:c.91+6T>C		intron variant
NM_001407950.1:c.91+6T>C		intron variant
NM_001407951.1:c.91+6T>C		intron variant
NM_001407952.1:c.91+6T>C		intron variant
NM_001407953.1:c.91+6T>C		intron variant
NM_001407954.1:c.91+6T>C		intron variant
NM_001407955.1:c.91+6T>C		intron variant
NM_001407956.1:c.91+6T>C		intron variant
NM_001407957.1:c.91+6T>C		intron variant
NM_001407958.1:c.91+6T>C		intron variant
NM_001407959.1:c.-81+6T>C		intron variant
NM_001407960.1:c.-81+6T>C		intron variant
NM_001407962.1:c.-81+6T>C		intron variant
NM_001407963.1:c.-81+6T>C		intron variant
NM_001407964.1:c.160+6T>C		intron variant
NM_001407965.1:c.-81+6T>C		intron variant
NM_001407966.1:c.-218-10002T>C		intron variant
NM_001407967.1:c.-218-10002T>C		intron variant
NM_001407968.1:c.301+6T>C		intron variant
NM_001407969.1:c.301+6T>C		intron variant
NM_001407970.1:c.301+6T>C		intron variant
NM_001407971.1:c.301+6T>C		intron variant
NM_001407972.1:c.301+6T>C		intron variant
NM_001407973.1:c.301+6T>C		intron variant
NM_001407974.1:c.301+6T>C		intron variant
NM_001407975.1:c.301+6T>C		intron variant
NM_001407976.1:c.301+6T>C		intron variant
NM_001407977.1:c.301+6T>C		intron variant
NM_001407978.1:c.301+6T>C		intron variant
NM_001407979.1:c.301+6T>C		intron variant
NM_001407980.1:c.301+6T>C		intron variant
NM_001407981.1:c.301+6T>C		intron variant
NM_001407982.1:c.301+6T>C		intron variant
NM_001407983.1:c.301+6T>C		intron variant
NM_001407984.1:c.301+6T>C		intron variant
NM_001407985.1:c.301+6T>C		intron variant
NM_001407986.1:c.301+6T>C		intron variant
NM_001407990.1:c.301+6T>C		intron variant
NM_001407991.1:c.301+6T>C		intron variant
NM_001407992.1:c.301+6T>C		intron variant
NM_001407993.1:c.301+6T>C		intron variant
NM_001408392.1:c.301+6T>C		intron variant
NM_001408396.1:c.301+6T>C		intron variant
NM_001408397.1:c.301+6T>C		intron variant
NM_001408398.1:c.301+6T>C		intron variant
NM_001408399.1:c.301+6T>C		intron variant
NM_001408400.1:c.301+6T>C		intron variant
NM_001408401.1:c.301+6T>C		intron variant
NM_001408402.1:c.301+6T>C		intron variant
NM_001408403.1:c.301+6T>C		intron variant
NM_001408404.1:c.301+6T>C		intron variant
NM_001408406.1:c.301+6T>C		intron variant
NM_001408407.1:c.301+6T>C		intron variant
NM_001408408.1:c.292+15T>C		intron variant
NM_001408409.1:c.223+6T>C		intron variant
NM_001408410.1:c.160+6T>C		intron variant
NM_001408411.1:c.223+6T>C		intron variant
NM_001408412.1:c.223+6T>C		intron variant
NM_001408413.1:c.223+6T>C		intron variant
NM_001408414.1:c.223+6T>C		intron variant
NM_001408415.1:c.223+6T>C		intron variant
NM_001408416.1:c.223+6T>C		intron variant
NM_001408418.1:c.301+6T>C		intron variant
NM_001408419.1:c.301+6T>C		intron variant
NM_001408420.1:c.301+6T>C		intron variant
NM_001408421.1:c.301+6T>C		intron variant
NM_001408422.1:c.301+6T>C		intron variant
NM_001408423.1:c.301+6T>C		intron variant
NM_001408424.1:c.301+6T>C		intron variant
NM_001408425.1:c.301+6T>C		intron variant
NM_001408426.1:c.301+6T>C		intron variant
NM_001408427.1:c.301+6T>C		intron variant
NM_001408428.1:c.301+6T>C		intron variant
NM_001408429.1:c.301+6T>C		intron variant
NM_001408430.1:c.301+6T>C		intron variant
NM_001408431.1:c.301+6T>C		intron variant
NM_001408432.1:c.301+6T>C		intron variant
NM_001408433.1:c.301+6T>C		intron variant
NM_001408434.1:c.301+6T>C		intron variant
NM_001408435.1:c.301+6T>C		intron variant
NM_001408436.1:c.301+6T>C		intron variant
NM_001408437.1:c.301+6T>C		intron variant
NM_001408438.1:c.301+6T>C		intron variant
NM_001408439.1:c.301+6T>C		intron variant
NM_001408440.1:c.301+6T>C		intron variant
NM_001408441.1:c.301+6T>C		intron variant
NM_001408442.1:c.301+6T>C		intron variant
NM_001408443.1:c.301+6T>C		intron variant
NM_001408444.1:c.301+6T>C		intron variant
NM_001408445.1:c.301+6T>C		intron variant
NM_001408446.1:c.301+6T>C		intron variant
NM_001408447.1:c.301+6T>C		intron variant
NM_001408448.1:c.301+6T>C		intron variant
NM_001408450.1:c.301+6T>C		intron variant
NM_001408451.1:c.169+6T>C		intron variant
NM_001408452.1:c.160+6T>C		intron variant
NM_001408453.1:c.160+6T>C		intron variant
NM_001408454.1:c.160+6T>C		intron variant
NM_001408455.1:c.160+6T>C		intron variant
NM_001408456.1:c.160+6T>C		intron variant
NM_001408457.1:c.160+6T>C		intron variant
NM_001408458.1:c.160+6T>C		intron variant
NM_001408459.1:c.160+6T>C		intron variant
NM_001408460.1:c.160+6T>C		intron variant
NM_001408461.1:c.160+6T>C		intron variant
NM_001408462.1:c.160+6T>C		intron variant
NM_001408463.1:c.160+6T>C		intron variant
NM_001408464.1:c.160+6T>C		intron variant
NM_001408465.1:c.160+6T>C		intron variant
NM_001408466.1:c.160+6T>C		intron variant
NM_001408467.1:c.160+6T>C		intron variant
NM_001408468.1:c.160+6T>C		intron variant
NM_001408469.1:c.160+6T>C		intron variant
NM_001408470.1:c.160+6T>C		intron variant
NM_001408472.1:c.301+6T>C		intron variant
NM_001408473.1:c.301+6T>C		intron variant
NM_001408474.1:c.223+6T>C		intron variant
NM_001408475.1:c.223+6T>C		intron variant
NM_001408476.1:c.223+6T>C		intron variant
NM_001408478.1:c.91+6T>C		intron variant
NM_001408479.1:c.91+6T>C		intron variant
NM_001408480.1:c.91+6T>C		intron variant
NM_001408481.1:c.91+6T>C		intron variant
NM_001408482.1:c.91+6T>C		intron variant
NM_001408483.1:c.91+6T>C		intron variant
NM_001408484.1:c.91+6T>C		intron variant
NM_001408485.1:c.91+6T>C		intron variant
NM_001408489.1:c.91+6T>C		intron variant
NM_001408490.1:c.91+6T>C		intron variant
NM_001408491.1:c.91+6T>C		intron variant
NM_001408492.1:c.91+6T>C		intron variant
NM_001408493.1:c.91+6T>C		intron variant
NM_001408494.1:c.301+6T>C		intron variant
NM_001408495.1:c.301+6T>C		intron variant
NM_001408496.1:c.160+6T>C		intron variant
NM_001408497.1:c.160+6T>C		intron variant
NM_001408498.1:c.160+6T>C		intron variant
NM_001408499.1:c.160+6T>C		intron variant
NM_001408500.1:c.160+6T>C		intron variant
NM_001408501.1:c.160+6T>C		intron variant
NM_001408502.1:c.91+6T>C		intron variant
NM_001408503.1:c.160+6T>C		intron variant
NM_001408504.1:c.160+6T>C		intron variant
NM_001408505.1:c.160+6T>C		intron variant
NM_001408506.1:c.91+6T>C		intron variant
NM_001408507.1:c.91+6T>C		intron variant
NM_001408508.1:c.91+6T>C		intron variant
NM_001408509.1:c.91+6T>C		intron variant
NM_001408510.1:c.-81+6T>C		intron variant
NM_001408511.1:c.160+6T>C		intron variant
NM_001408512.1:c.-81+6T>C		intron variant
NM_001408513.1:c.91+6T>C		intron variant
NM_001408514.1:c.91+6T>C		intron variant
NM_007297.4:c.160+6T>C		intron variant
NM_007298.4:c.301+6T>C		intron variant
NM_007299.4:c.301+6T>C		intron variant
NM_007300.4:c.301+6T>C		intron variant
NC_000017.11:g.43104862A>G
NC_000017.10:g.41256879A>G
NG_005905.2:g.113122T>C
LRG_292:g.113122T>C
LRG_292t1:c.301+6T>C

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000017.11:43104861:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

functionally_abnormal; Sequence Ontology [ SO:0002218]

The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.301+6T>C, a SPLICE REGION variant, produced a function score of -1.95, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: â€˜functionalâ€™, score > -0.748; â€˜intermediateâ€™, -0.748 > score > -1.328; â€˜non-functionalâ€™, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00001

Exome Aggregation Consortium (ExAC) 0.00002

Trans-Omics for Precision Medicine (TOPMed) 0.00002

Links

ClinGen: CA055594 dbSNP: rs753859240 VarSome

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
Gene	OMIM	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.
Hereditary cancer-predisposing syndrome	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Apr 27, 2023	RCV000584261.8
Hereditary breast ovarian cancer syndrome	Uncertain significance (1)	criteria provided, single submitter	Dec 22, 2023	RCV000234331.11
Breast-ovarian cancer, familial, susceptibility to, 1	Conflicting interpretations of pathogenicity (6)	criteria provided, conflicting classifications	Apr 12, 2024	RCV000210142.10
Breast-ovarian cancer, familial, susceptibility to, 1 Familial cancer of breast Fanconi anemia, complementation group S Pancreatic cancer, susceptibility to, 4	Uncertain significance (1)	criteria provided, single submitter	Mar 16, 2022	RCV002478759.1
not provided	Uncertain significance (1)	criteria provided, single submitter	Dec 12, 2023	RCV003159109.2
not specified	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Jan 31, 2019	RCV000507484.4

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.
Uncertain significance (Oct 29, 2021)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV004915381.1 First in ClinVar: May 01, 2024 Last updated: May 01, 2024	Comment: The c.301+6T>C intronic alteration consists of a T to C substitution nucleotides after coding exon 4 in the BRCA1 gene. Based on insufficient or conflicting … (more) The c.301+6T>C intronic alteration consists of a T to C substitution nucleotides after coding exon 4 in the BRCA1 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
Uncertain significance (Apr 07, 2024)	criteria provided, single submitter (St. Jude Assertion Criteria 2020) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: germline	St. Jude Molecular Pathology, St. Jude Children's Research Hospital Accession: SCV005402395.1 First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024	Comment: The BRCA1 c.301+6T>C intronic change results in a T to C substitution at the +6 position of intron 5 of the BRCA1 gene. Algorithms that … (more) The BRCA1 c.301+6T>C intronic change results in a T to C substitution at the +6 position of intron 5 of the BRCA1 gene. Algorithms that predict the impact of sequence changes on splicing indicate that this change may impact splicing. A published RNA study reports this variant is associated with very low levels of aberrant transcript (PMID: 21769658). This variant has a maximum subpopulation frequency of 0.002% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). This variant has been reported in individuals with breast and/or ovarian cancer (PMID: 21769658, 26845104). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.? (less)
Likely pathogenic (Apr 12, 2024)	criteria provided, single submitter (Dawood et al. (medRxiv. 2024)) Method: curation	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: germline	Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine Accession: SCV005402496.1 First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024	Publications: PubMed (2) PubMed: 39142283‚ 34793697 DOI: 10.1101/2024.04.11.24305690 DOI: 10.1101/2024.04.11.24305690 Comment: Each variant was annotated with functional scores from MAVE data which was translated into functional evidence codes. All other evidence codes and combining criteria were … (more) Each variant was annotated with functional scores from MAVE data which was translated into functional evidence codes. All other evidence codes and combining criteria were adhered to as closely as possible based on the ClinGen VCEP (Variant Curation Expert Panel) gene-specific recommendations. See Supplemental Figure 34 of final paper (Supp Fig. 28 in preprint: doi:10.1101/2024.04.11.24305690) for a table to see which lines of evidence we did not have data for. The ClinGen VCEPs are highly regarded as the gold-standard for gene-specific variant curation and are developed after extensive evaluation of the evidence by clinical and scientific experts for the particular gene to classify genomic variants on a spectrum from pathogenic to benign using the 2015 ACMG/AMP Variant Interpretation Guidelines as a backbone (PMID: 25741868). Reclassification of these VUS variants from gnomAD or All of Us focused only on variants originally prescribed as VUS in ClinVar. To ensure reproducibility, transparency, and increased throughput, all the procedures for annotating variants and assigning evidence codes were codified using Python. All code has been made freely available and is linked in the Code Availability section and all reclassified variants with evidence codes used can be found in Tables S18-19 (preprint: doi:10.1101/2024.04.11.24305690). For the MAVE data, the clinical curation and clinical strength assignment as per the ClinGen recommendations in Brnich et al. (2020) (PMID: 31892348) for or against pathogenicity or benignity of each of these MAVE datasets utilized in this study were previously published in Fayer et al. (2021) (PMID: 34793697).In brief, for BRCA1 variants, if a variant was categorized as FUNC (functional), it was assigned BS3 evidence and no PS3 evidence, whereas if it was categorized as LOF (loss of function), the variant was assigned PS3 evidence and no BS3 evidence. Variants categorized as INT (intermediate) were left unannotated. For the BRCA1 combining criteria, greater than or equal to 1 criteria of strong benign evidence was enough to reclassify the VUS as Likely Benign. This variant GRCh38:17:43104862:A>G was assigned evidence codes ['PS3', 'PP3', 'PM2_Supporting'] and an overall classification of Likely pathogenic (less)
Uncertain significance (Nov 20, 2015)	criteria provided, single submitter (Shirts et al. (Genet Med 2016)) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: yes Allele origin: germline	University of Washington Department of Laboratory Medicine, University of Washington Accession: SCV000266156.1 First in ClinVar: Mar 20, 2016 Last updated: Mar 20, 2016	Number of individuals with the variant: 1 Clinical Features: ovarian cancer (present) Age: 60-69 years
Uncertain significance (Mar 16, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) 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: SCV002784813.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Uncertain significance (Dec 12, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV003852908.2 First in ClinVar: Apr 09, 2023 Last updated: Sep 16, 2024	Comment: Observed in individuals with a personal or family history of breast and/or ovarian cancer (PMID: 21769658, 26845104, 34178674); Published functional studies are conflicting: variant classified … (more) Observed in individuals with a personal or family history of breast and/or ovarian cancer (PMID: 21769658, 26845104, 34178674); Published functional studies are conflicting: variant classified as non-functional based on a saturation genome editing (SGE) assay measuring cell survival (PMID: 30209399); an RNA study detected very low levels of aberrant transcript predicted to encode an in-frame change of four amino acids (p.Gly98_Tyr101delinsAsp); however, multifactorial likelihood analysis incorporating these splicing data resulted in classification of this variant as not pathogenic/low clinical significance (PMID: 21769658); Classified as benign (IARC class 1) in one multi-factorial likelihood assessment utilizing co-segregation, family history, and co-occurrence data, but specific clinical details were not provided (PMID: 34597585); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Also known as IVS6+6T>C and 420+6T>C; This variant is associated with the following publications: (PMID: 26913838, 26845104, 21769658, 34178674, 29750258, 23893897, 20858050, 30209399, Findlay2023[interimreport], 34597585) (less)
Uncertain significance (Mar 25, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004215127.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024
Uncertain significance (Jan 31, 2019)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000698994.2 First in ClinVar: Mar 17, 2018 Last updated: Nov 08, 2019	Publications: PubMed (7) PubMed: 20858050‚ 21769658‚ 23893897‚ 26845104‚ 26913838‚ 29750258‚ 30209399 Comment: Variant summary: BRCA1 c.301+6T>C alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly … (more) Variant summary: BRCA1 c.301+6T>C alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Three predict the variant weakens a 5' donor site. One predicts that the variant abolishes a 5' splicing donor site. This is supoprted by a study reporting very low levels of aberrant transcript, possibly resulting from use of a cryptic site at c.292, 9 nucleotides upstream from canonical 5' splice donor site (Thomassen_2011). The variant allele was found at a frequency of 1.2e-05 in 245948 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.301+6T>C has been reported in the literature in an individual affected with ovary cancer (Shirts_2015) and in an individual affected with breast cancer and with a family history of breast and ovarian cancer and other cancers including lung cancer, layrynx cancer and myeloma however, without evidence of co-segregation of the variant with disease (Thomassen_2011). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Experimental evidence evaluating an impact on protein function through assessment of functional homology-directed DNA repair (HDR) pathway reported the variant with a functional score supporting loss of function (Findlay_2018). Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
Uncertain significance (Nov 29, 2016)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000600312.2 First in ClinVar: Sep 30, 2017 Last updated: Jan 01, 2022	Publications: PubMed (3) PubMed: 21769658‚ 26913838‚ 26845104
Uncertain significance (Apr 27, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000688411.5 First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024	Publications: PubMed (3) PubMed: 21769658‚ 26845104‚ 30209399 Comment: This variant causes a T to C nucleotide substitution at the +6 position of intron 5 of the BRCA1 gene. An RNA study has reported … (more) This variant causes a T to C nucleotide substitution at the +6 position of intron 5 of the BRCA1 gene. An RNA study has reported a very low level of aberrant splicing product lacking the last nine nucleotides of exon 5 predicted to result in an in-frame deletion of three amino acids (PMID: 21769658). A functional study has reported that this variant disrupts BRCA1 function in a haploid cell proliferation assay (PMID: 30209399). This variant has been reported in two individuals affected with breast or ovarian cancer (PMID: 21769658, 26845104). This variant has been identified in 3/251174 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Uncertain significance (Dec 22, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000289768.9 First in ClinVar: Jul 01, 2016 Last updated: Feb 14, 2024	Publications: PubMed (5) PubMed: 21769658‚ 26845104‚ 34178674‚ 17576681‚ 9536098 Comment: This sequence change falls in intron 5 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein. … (more) This sequence change falls in intron 5 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in the loss of 3 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is present in population databases (rs753859240, gnomAD 0.002%). This variant has been observed in individual(s) with breast cancer and ovarian cancer (PMID: 21769658, 26845104, 34178674). ClinVar contains an entry for this variant (Variation ID: 224562). Based on a multifactorial likelihood algorithm using genetic, in silico, and/or statistical data, this variant has been determined to have a low probability of being pathogenic (PMID: 21769658). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in the activation of a cryptic splice site in exon 5 (PMID: 21769658; Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Benign (Sep 01, 2023)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: yes Allele origin: germline	Department of Medical and Surgical Sciences, University of Bologna Accession: SCV004228313.1 First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024	Comment: PM2(Supporting)+PP3(Supporting)+BS3(Strong)+BP5(Very Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
not provided (-)	no classification provided Method: in vitro	Breast-ovarian cancer, familial 1 Affected status: not applicable Allele origin: not applicable	Brotman Baty Institute, University of Washington Accession: SCV001238610.1 First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020	Publications: PubMed (1) PubMed: 30209399 Other databases https://sge.gs.washington.edu/BR… https://sge.gs.washington.edu/BRCA1/ Method: saturation genome editing in haploid cells Result: LOSS_OF_FUNCTION:-1.94892155071841
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Comment:

The BRCA1 c.301+6T>C intronic change results in a T to C substitution at the +6 position of intron 5 of the BRCA1 gene. Algorithms that predict the impact of sequence changes on splicing indicate that this change may impact splicing. A published RNA study reports this variant is associated with very low levels of aberrant transcript (PMID: 21769658). This variant has a maximum subpopulation frequency of 0.002% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). This variant has been reported in individuals with breast and/or ovarian cancer (PMID: 21769658, 26845104). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.?

Comment:

Each variant was annotated with functional scores from MAVE data which was translated into functional evidence codes. All other evidence codes and combining criteria were adhered to as closely as possible based on the ClinGen VCEP (Variant Curation Expert Panel) gene-specific recommendations. See Supplemental Figure 34 of final paper (Supp Fig. 28 in preprint: doi:10.1101/2024.04.11.24305690) for a table to see which lines of evidence we did not have data for. The ClinGen VCEPs are highly regarded as the gold-standard for gene-specific variant curation and are developed after extensive evaluation of the evidence by clinical and scientific experts for the particular gene to classify genomic variants on a spectrum from pathogenic to benign using the 2015 ACMG/AMP Variant Interpretation Guidelines as a backbone (PMID: 25741868). Reclassification of these VUS variants from gnomAD or All of Us focused only on variants originally prescribed as VUS in ClinVar. To ensure reproducibility, transparency, and increased throughput, all the procedures for annotating variants and assigning evidence codes were codified using Python. All code has been made freely available and is linked in the Code Availability section and all reclassified variants with evidence codes used can be found in Tables S18-19 (preprint: doi:10.1101/2024.04.11.24305690). For the MAVE data, the clinical curation and clinical strength assignment as per the ClinGen recommendations in Brnich et al. (2020) (PMID: 31892348) for or against pathogenicity or benignity of each of these MAVE datasets utilized in this study were previously published in Fayer et al. (2021) (PMID: 34793697).In brief, for BRCA1 variants, if a variant was categorized as FUNC (functional), it was assigned BS3 evidence and no PS3 evidence, whereas if it was categorized as LOF (loss of function), the variant was assigned PS3 evidence and no BS3 evidence. Variants categorized as INT (intermediate) were left unannotated. For the BRCA1 combining criteria, greater than or equal to 1 criteria of strong benign evidence was enough to reclassify the VUS as Likely Benign. This variant GRCh38:17:43104862:A>G was assigned evidence codes ['PS3', 'PP3', 'PM2_Supporting'] and an overall classification of Likely pathogenic

Comment:

Observed in individuals with a personal or family history of breast and/or ovarian cancer (PMID: 21769658, 26845104, 34178674); Published functional studies are conflicting: variant classified as non-functional based on a saturation genome editing (SGE) assay measuring cell survival (PMID: 30209399); an RNA study detected very low levels of aberrant transcript predicted to encode an in-frame change of four amino acids (p.Gly98_Tyr101delinsAsp); however, multifactorial likelihood analysis incorporating these splicing data resulted in classification of this variant as not pathogenic/low clinical significance (PMID: 21769658); Classified as benign (IARC class 1) in one multi-factorial likelihood assessment utilizing co-segregation, family history, and co-occurrence data, but specific clinical details were not provided (PMID: 34597585); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Also known as IVS6+6T>C and 420+6T>C; This variant is associated with the following publications: (PMID: 26913838, 26845104, 21769658, 34178674, 29750258, 23893897, 20858050, 30209399, Findlay2023[interimreport], 34597585)

Comment:

Variant summary: BRCA1 c.301+6T>C alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Three predict the variant weakens a 5' donor site. One predicts that the variant abolishes a 5' splicing donor site. This is supoprted by a study reporting very low levels of aberrant transcript, possibly resulting from use of a cryptic site at c.292, 9 nucleotides upstream from canonical 5' splice donor site (Thomassen_2011). The variant allele was found at a frequency of 1.2e-05 in 245948 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.301+6T>C has been reported in the literature in an individual affected with ovary cancer (Shirts_2015) and in an individual affected with breast cancer and with a family history of breast and ovarian cancer and other cancers including lung cancer, layrynx cancer and myeloma however, without evidence of co-segregation of the variant with disease (Thomassen_2011). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Experimental evidence evaluating an impact on protein function through assessment of functional homology-directed DNA repair (HDR) pathway reported the variant with a functional score supporting loss of function (Findlay_2018). Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

Comment:

This variant causes a T to C nucleotide substitution at the +6 position of intron 5 of the BRCA1 gene. An RNA study has reported a very low level of aberrant splicing product lacking the last nine nucleotides of exon 5 predicted to result in an in-frame deletion of three amino acids (PMID: 21769658). A functional study has reported that this variant disrupts BRCA1 function in a haploid cell proliferation assay (PMID: 30209399). This variant has been reported in two individuals affected with breast or ovarian cancer (PMID: 21769658, 26845104). This variant has been identified in 3/251174 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

Comment:

This sequence change falls in intron 5 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in the loss of 3 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is present in population databases (rs753859240, gnomAD 0.002%). This variant has been observed in individual(s) with breast cancer and ovarian cancer (PMID: 21769658, 26845104, 34178674). ClinVar contains an entry for this variant (Variation ID: 224562). Based on a multifactorial likelihood algorithm using genetic, in silico, and/or statistical data, this variant has been determined to have a low probability of being pathogenic (PMID: 21769658). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in the activation of a cryptic splice site in exon 5 (PMID: 21769658; Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

PM2(Supporting)+PP3(Supporting)+BS3(Strong)+BP5(Very Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
functionally_abnormal (SO:0002218)	saturation genome editing in haploid cells Method citation(s): PubMed(1)	LOSS_OF_FUNCTION:-1.94892155071841	Brotman Baty Institute, University of Washington Accession: SCV001238610.1	Publications PubMed (1) Other databases https://sge.gs.washington.edu/BR… Comment: The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.301+6T>C, a SPLICE REGION variant, produced a function score of -1.95, corresponding to a functional classification of … (more) The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.301+6T>C, a SPLICE REGION variant, produced a function score of -1.95, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: â€˜functionalâ€™, score > -0.748; â€˜intermediateâ€™, -0.748 > score > -1.328; â€˜non-functionalâ€™, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Evidence-based recommendations for gene-specific ACMG/AMP variant classification from the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel.	Parsons MT	American journal of human genetics	2024	PMID: 39142283
Defining and Reducing Variant Classification Disparities.	Dawood M	medRxiv : the preprint server for health sciences	2024	DOI: 10.1101/2024.04.11.24305690
Closing the gap: Systematic integration of multiplexed functional data resolves variants of uncertain significance in BRCA1, TP53, and PTEN.	Fayer S	American journal of human genetics	2021	PMID: 34793697
Prevalence and Spectrum of Germline BRCA1 and BRCA2 Variants of Uncertain Significance in Breast/Ovarian Cancer: Mysterious Signals From the Genome.	Fanale D	Frontiers in oncology	2021	PMID: 34178674
Accurate classification of BRCA1 variants with saturation genome editing.	Findlay GM	Nature	2018	PMID: 30209399
Novel diagnostic tool for prediction of variant spliceogenicity derived from a set of 395 combined in silico/in vitro studies: an international collaborative effort.	Leman R	Nucleic acids research	2018	PMID: 29750258
Adding In Silico Assessment of Potential Splice Aberration to the Integrated Evaluation of BRCA Gene Unclassified Variants.	Vallée MP	Human mutation	2016	PMID: 26913838
Improving performance of multigene panels for genomic analysis of cancer predisposition.	Shirts BH	Genetics in medicine : official journal of the American College of Medical Genetics	2016	PMID: 26845104
Evaluation of a 5-tier scheme proposed for classification of sequence variants using bioinformatic and splicing assay data: inter-reviewer variability and promotion of minimum reporting guidelines.	Walker LC	Human mutation	2013	PMID: 23893897
Characterization of BRCA1 and BRCA2 splicing variants: a collaborative report by ENIGMA consortium members.	Thomassen M	Breast cancer research and treatment	2012	PMID: 21769658
A one-step prescreening for point mutations and large rearrangement in BRCA1 and BRCA2 genes using quantitative polymerase chain reaction and high-resolution melting curve analysis.	Coulet F	Genetic testing and molecular biomarkers	2010	PMID: 20858050
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.	Buratti E	Nucleic acids research	2007	PMID: 17576681
Statistical features of human exons and their flanking regions.	Zhang MQ	Human molecular genetics	1998	PMID: 9536098
https://sge.gs.washington.edu/BRCA1/	-	-	-	-
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Text-mined citations for rs753859240 ...

These 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

ClinVar Genomic variation as it relates to human health

NM_007294.4(BRCA1):c.301+6T>C

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs753859240 ...