ClinVar Genomic variation as it relates to human health
NM_004656.4(BAP1):c.1408G>A (p.Gly470Arg)
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.
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.
Uncertain significance(4); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004656.4(BAP1):c.1408G>A (p.Gly470Arg)
Variation ID: 133663 Accession: VCV000133663.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p21.1 3: 52403737 (GRCh38) [ NCBI UCSC ] 3: 52437753 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Jun 9, 2014 Feb 14, 2024 Jan 23, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004656.4:c.1408G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004647.1:p.Gly470Arg missense NC_000003.12:g.52403737C>T NC_000003.11:g.52437753C>T NG_031859.1:g.11257G>A LRG_529:g.11257G>A LRG_529t1:c.1408G>A - Protein change
- G470R
- Other names
- -
- Canonical SPDI
- NC_000003.12:52403736: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.
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0.00020 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00005
The Genome Aggregation Database (gnomAD), exomes 0.00007
The Genome Aggregation Database (gnomAD) 0.00012
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00041
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 | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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. |
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BAP1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2713 | 2729 |
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. |
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not provided (1) |
no classification provided
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Sep 19, 2013 | RCV000120191.1 | |
Uncertain significance (2) |
criteria provided, single submitter
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Jan 21, 2024 | RCV000471822.11 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Apr 4, 2023 | RCV000574998.9 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Sep 8, 2023 | RCV001527719.5 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 23, 2024 | RCV003492520.1 |
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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Likely benign
(Aug 11, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000902856.2
First in ClinVar: May 20, 2019 Last updated: Jan 08, 2022 |
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Uncertain significance
(Aug 31, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002537259.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Uncertain significance
(Jun 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001738846.4
First in ClinVar: Jul 07, 2021 Last updated: Mar 04, 2023 |
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with thyroid cancer and healthy individuals under age … (more)
In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with thyroid cancer and healthy individuals under age 50 undergoing whole genome sequencing (Bodian 2014, Yehia 2018); This variant is associated with the following publications: (PMID: 30480620, 24728327, 29684080) (less)
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Likely benign
(Apr 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000672757.5
First in ClinVar: Jan 01, 2018 Last updated: Jul 08, 2023 |
Comment:
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, … (more)
This alteration is classified as likely benign based on a combination of the following: 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)
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Uncertain significance
(Sep 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004220464.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
In the published literature, this variant has been reported in an individual with thyroid cancer (PMID: 29684080 (2018)), and in healthy individuals under the age … (more)
In the published literature, this variant has been reported in an individual with thyroid cancer (PMID: 29684080 (2018)), and in healthy individuals under the age of 50 (PMID: 24728327 (2014)). It has also been reported as a somatic variant in an individual with uveal melanoma (PMID: 30480620 (2019)). The frequency of this variant in the general population, 0.00023 (8/34582 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. (less)
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Likely benign
(Jan 23, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV000838038.3
First in ClinVar: Oct 10, 2018 Last updated: Feb 04, 2024 |
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Uncertain significance
(Jan 21, 2024)
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criteria provided, single submitter
Method: clinical testing
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BAP1-related tumor predisposition syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000553923.9
First in ClinVar: Apr 17, 2017 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 470 of the BAP1 protein (p.Gly470Arg). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 470 of the BAP1 protein (p.Gly470Arg). This variant is present in population databases (rs576538858, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with BAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 133663). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BAP1 protein function with a negative predictive value of 80%. 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)
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000084337.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 |
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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not provided
(-)
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no classification provided
Method: phenotyping only
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BAP1-related tumor predisposition syndrome
Affected status: unknown
Allele origin:
unknown
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GenomeConnect - Invitae Patient Insights Network
Accession: SCV004228670.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
Variant interpreted as Uncertain significance and reported on 10-22-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the … (more)
Variant interpreted as Uncertain significance and reported on 10-22-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Abnormality of vision (present) , Myopia (present) , Tinnitus (present) , Bruising susceptibility (present) , Epistaxis (present) , Abnormal erythrocyte morphology (present) , Autoimmunity (present) … (more)
Abnormality of vision (present) , Myopia (present) , Tinnitus (present) , Bruising susceptibility (present) , Epistaxis (present) , Abnormal erythrocyte morphology (present) , Autoimmunity (present) , Abnormal inflammatory response (present) , Obesity (present) , Increased susceptibility to fractures (present) , Delayed puberty (present) , Abnormality of the parathyroid physiology (present) , Abnormality of the bladder (present) , Abnormality of the female genitalia (present) (less)
Indication for testing: Presymptomatic, Family Testing
Age: 60-69 years
Sex: female
Method: Gene Panel Sequencing
Testing laboratory: Invitae
Date variant was reported to submitter: 2019-10-22
Testing laboratory interpretation: Uncertain significance
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Molecular and immunohistochemical analyses of uveal melanoma patient cohort. | Sarubi HC | Melanoma research | 2019 | PMID: 30480620 |
Unexpected cancer-predisposition gene variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome patients without underlying germline PTEN mutations. | Yehia L | PLoS genetics | 2018 | PMID: 29684080 |
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
Text-mined citations for rs576538858 ...
HelpRecord last updated Feb 20, 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.