ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4987-7A>G

dbSNP: rs1025136518
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001219567 SCV001391512 uncertain significance Hereditary breast ovarian cancer syndrome 2019-07-04 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with BRCA1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 15 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein.
Ambry Genetics RCV002339372 SCV002643514 likely pathogenic Hereditary cancer-predisposing syndrome 2024-04-25 criteria provided, single submitter clinical testing The c.4987-7A>G intronic variant results from an A to G substitution 7 nucleotides upstream from coding exon 15 in the BRCA1 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and may result in the creation or strengthening of a novel splice acceptor site that is predicted to a lead to a small, in frame insertion of two amino acids. One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay. (Findlay GM et al. Nature, 2018 10;562:217-222). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Brotman Baty Institute, University of Washington RCV001077402 SCV001243328 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro

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