Variant summary: BBS1 c.1447C>T (p.Arg483X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 240090 control chromosomes (gnomAD). c.1447C>T has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (BEales_2003, Deveault_2011, gerth_2008, Jacobson_2014, Muller_2010). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
ClinVar Genomic variation as it relates to human health
NM_024649.5(BBS1):c.1447C>T (p.Arg483Ter)
Germline
Classification
Help
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.
(8)
Help
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.
Pathogenic
8
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_024649.5(BBS1):c.1447C>T (p.Arg483Ter)
Variation ID: 649714 Accession: VCV000649714.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.2 11: 66529926 (GRCh38) [ NCBI UCSC ] 11: 66297397 (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 Aug 14, 2019 Dec 28, 2024 Mar 20, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_024649.5:c.1447C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_078925.3:p.Arg483Ter nonsense NM_001348571.2:c.560-438G>A intron variant NC_000011.10:g.66529926C>T NC_000011.9:g.66297397C>T NG_009093.1:g.24279C>T - Protein change
- R483*
- Other names
- -
- Canonical SPDI
- NC_000011.10:66529925:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
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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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
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The Genome Aggregation Database (gnomAD) 0.00001
- 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. |
|||
| BBS1 | - | - |
GRCh38 GRCh37 |
460 | 1132 | |
| ZDHHC24 | - | - | - |
GRCh38 GRCh37 |
17 | 687 |
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. |
|---|---|---|---|---|
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 8, 2023 | RCV000804705.18 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Mar 20, 2024 | RCV001273360.12 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Aug 16, 2022 | RCV003128709.8 | |
| Pathogenic (1) |
criteria provided, single submitter
|
May 10, 2022 | RCV002534792.9 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jan 1, 2012 | RCV004818039.1 |
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. |
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|---|---|---|---|---|---|
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Pathogenic
(Nov 22, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Bardet-Biedl syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001362213.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: BBS1 c.1447C>T (p.Arg483X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BBS1 c.1447C>T (p.Arg483X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 240090 control chromosomes (gnomAD). c.1447C>T has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (BEales_2003, Deveault_2011, gerth_2008, Jacobson_2014, Muller_2010). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Sep 08, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Bardet-Biedl syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000944627.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg483*) in the BBS1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg483*) in the BBS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS1 are known to be pathogenic (PMID: 12118255, 21520335, 27032803). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 12677556). ClinVar contains an entry for this variant (Variation ID: 649714). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Mar 08, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Bardet-Biedl syndrome 1
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002781248.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
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Pathogenic
(Aug 16, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV003805361.1
First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023 |
Comment:
Identified with a second BBS1 variant in multiple individuals with clinical features of Bardet-Biedl syndrome in published literature (Gerth et al., 2008; Muller et al., … (more)
Identified with a second BBS1 variant in multiple individuals with clinical features of Bardet-Biedl syndrome in published literature (Gerth et al., 2008; Muller et al., 2010; Deveault et al., 2011; Jacobson et al., 2014; Grudzinska Pechhacker et al., 2021); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 17980398, 20177705, 25074776, 21344540, 12677556, 34940782) (less)
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Pathogenic
(May 10, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV003601797.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.1447C>T (p.R483*) alteration, located in exon 14 (coding exon 14) of the BBS1 gene, consists of a C to T substitution at nucleotide position … (more)
The c.1447C>T (p.R483*) alteration, located in exon 14 (coding exon 14) of the BBS1 gene, consists of a C to T substitution at nucleotide position 1447. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 483. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of 0.001% (3/240090) total alleles studied. The highest observed frequency was 0.003% (3/111230) of European (non-Finnish) alleles. This alteration has been detected in conjunction with another BBS1 pathogenic mutation in multiple individuals with features of BBS1-related Bardet-Biedl syndrome (Muller, 2010; Garth, 2008; Deveault, 2011; Kerr, 2016; Beales, 2003). Based on the available evidence, this alteration is classified as pathogenic. (less)
|
|
|
Pathogenic
(Mar 20, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Bardet-Biedl syndrome 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004217374.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Jan 01, 2012)
|
criteria provided, single submitter
Method: clinical testing
|
Retinal dystrophy
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg
Accession: SCV005072130.1
First in ClinVar: Dec 28, 2024 Last updated: Dec 28, 2024 |
|
|
|
Pathogenic
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Bardet-Biedl syndrome type 1
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001456340.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Arg483*) in the BBS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS1 are known to be pathogenic (PMID: 12118255, 21520335, 27032803). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 12677556). ClinVar contains an entry for this variant (Variation ID: 649714). For these reasons, this variant has been classified as Pathogenic.
Comment:
Identified with a second BBS1 variant in multiple individuals with clinical features of Bardet-Biedl syndrome in published literature (Gerth et al., 2008; Muller et al., 2010; Deveault et al., 2011; Jacobson et al., 2014; Grudzinska Pechhacker et al., 2021); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 17980398, 20177705, 25074776, 21344540, 12677556, 34940782)
Comment:
The c.1447C>T (p.R483*) alteration, located in exon 14 (coding exon 14) of the BBS1 gene, consists of a C to T substitution at nucleotide position 1447. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 483. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of 0.001% (3/240090) total alleles studied. The highest observed frequency was 0.003% (3/111230) of European (non-Finnish) alleles. This alteration has been detected in conjunction with another BBS1 pathogenic mutation in multiple individuals with features of BBS1-related Bardet-Biedl syndrome (Muller, 2010; Garth, 2008; Deveault, 2011; Kerr, 2016; Beales, 2003). Based on the available evidence, this alteration is classified as pathogenic.
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:
Variant summary: BBS1 c.1447C>T (p.Arg483X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 240090 control chromosomes (gnomAD). c.1447C>T has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (BEales_2003, Deveault_2011, gerth_2008, Jacobson_2014, Muller_2010). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Arg483*) in the BBS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS1 are known to be pathogenic (PMID: 12118255, 21520335, 27032803). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 12677556). ClinVar contains an entry for this variant (Variation ID: 649714). For these reasons, this variant has been classified as Pathogenic.
Comment:
Identified with a second BBS1 variant in multiple individuals with clinical features of Bardet-Biedl syndrome in published literature (Gerth et al., 2008; Muller et al., 2010; Deveault et al., 2011; Jacobson et al., 2014; Grudzinska Pechhacker et al., 2021); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 17980398, 20177705, 25074776, 21344540, 12677556, 34940782)
Comment:
The c.1447C>T (p.R483*) alteration, located in exon 14 (coding exon 14) of the BBS1 gene, consists of a C to T substitution at nucleotide position 1447. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 483. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, the T allele has an overall frequency of 0.001% (3/240090) total alleles studied. The highest observed frequency was 0.003% (3/111230) of European (non-Finnish) alleles. This alteration has been detected in conjunction with another BBS1 pathogenic mutation in multiple individuals with features of BBS1-related Bardet-Biedl syndrome (Muller, 2010; Garth, 2008; Deveault, 2011; Kerr, 2016; Beales, 2003). Based on the available evidence, this alteration is classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Genetic epidemiology of inherited retinal diseases in a large patient cohort followed at a single center in Italy. | Karali M | Scientific reports | 2022 | PMID: 36460718 |
| Comprehensive analysis of recessive carrier status using exome and genome sequencing data in 1543 Southern Chinese. | Chau JFT | NPJ genomic medicine | 2022 | PMID: 35314707 |
| Comparative Natural History of Visual Function From Patients With Biallelic Variants in BBS1 and BBS10. | Grudzinska Pechhacker MK | Investigative ophthalmology & visual science | 2021 | PMID: 34940782 |
| Improving the management of Inherited Retinal Dystrophies by targeted sequencing of a population-specific gene panel. | Bravo-Gil N | Scientific reports | 2016 | PMID: 27032803 |
| Exploration of the cognitive, adaptive and behavioral functioning of patients affected with Bardet-Biedl syndrome. | Kerr EN | Clinical genetics | 2016 | PMID: 25988237 |
| RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
| TULP1 mutations causing early-onset retinal degeneration: preserved but insensitive macular cones. | Jacobson SG | Investigative ophthalmology & visual science | 2014 | PMID: 25074776 |
| U1 snRNA-mediated gene therapeutic correction of splice defects caused by an exceptionally mild BBS mutation. | Schmid F | Human mutation | 2011 | PMID: 21520335 |
| BBS genotype-phenotype assessment of a multiethnic patient cohort calls for a revision of the disease definition. | Deveault C | Human mutation | 2011 | PMID: 21344540 |
| Identification of 28 novel mutations in the Bardet-Biedl syndrome genes: the burden of private mutations in an extensively heterogeneous disease. | Muller J | Human genetics | 2010 | PMID: 20177705 |
| Retinal morphology in patients with BBS1 and BBS10 related Bardet-Biedl Syndrome evaluated by Fourier-domain optical coherence tomography. | Gerth C | Vision research | 2008 | PMID: 17980398 |
| Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome. | Beales PL | American journal of human genetics | 2003 | PMID: 12677556 |
| Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome. | Mykytyn K | Nature genetics | 2002 | PMID: 12118255 |
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Text-mined citations for rs745656125 ...
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the rs number, so they may include citations for more than one variant
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variant of interest.
Record last updated Jan 13, 2025
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.