ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.736A>G (p.Ile246Val)

gnomAD frequency: 0.00002  dbSNP: rs376893571
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000534123 SCV000633711 likely benign Familial cancer of breast; Fanconi anemia complementation group J 2025-01-29 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000580310 SCV000684301 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-15 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 246 of the BRIP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast and/or ovarian cancer (PMID: 28796317). This variant has been identified in 39/251202 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759716 SCV000889225 likely benign not provided 2023-09-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000580310 SCV001188689 likely benign Hereditary cancer-predisposing syndrome 2022-10-03 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
Illumina Laboratory Services, Illumina RCV001125840 SCV001284963 uncertain significance Fanconi anemia complementation group J 2017-08-22 criteria provided, single submitter clinical testing 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Sema4, Sema4 RCV000580310 SCV002533740 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-22 criteria provided, single submitter curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV003324713 SCV004030447 uncertain significance Familial cancer of breast 2023-08-29 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 246 of the BRIP1 protein (p.Ile246Val). This variant is present in population databases (rs376893571, gnomAD 0.1%). This missense change has been observed in individual(s) with breast cancer (PMID: 28796317). ClinVar contains an entry for this variant (Variation ID: 461180). This amino acid position is highly conservative (PhyloP=7.41) . In silico prediction is inconclusive . 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.
GeneDx RCV000759716 SCV004170245 likely benign not provided 2023-04-20 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28796317, 29641532, 32164585)
Baylor Genetics RCV003324713 SCV004211343 uncertain significance Familial cancer of breast 2024-01-18 criteria provided, single submitter clinical testing

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