ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.2906-1G>A

gnomAD frequency: 0.00001  dbSNP: rs773639563
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000989987 SCV001140749 likely pathogenic Familial cancer of breast 2019-05-28 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001182221 SCV001347580 likely pathogenic Hereditary cancer-predisposing syndrome 2019-05-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001858716 SCV002155466 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2023-12-01 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 19 of the BRIP1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (rs773639563, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with thyroid carcinoma (PMID: 29625052). ClinVar contains an entry for this variant (Variation ID: 803448). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Ambry Genetics RCV001182221 SCV005101026 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-18 criteria provided, single submitter clinical testing The c.2906-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 19 of the BRIP1 gene. 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; however, direct evidence is insufficient at this time (Ambry internal data). The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay; however, direct evidence is unavailable. The exact functional effect of the altered amino acid sequence is unknown. This nucleotide position is highly conserved in available vertebrate species. Based on the available evidence, the clinical significance of this variant remains unclear.
GeneDx RCV004721693 SCV005326577 uncertain significance not provided 2024-01-23 criteria provided, single submitter clinical testing Canonical splice site variant with an unclear effect on protein function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29625052, 29922827, 36451132)

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