ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.80+1G>C

dbSNP: rs80358010
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000111705 SCV000326415 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2015-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509617 SCV000607774 pathogenic Hereditary cancer-predisposing syndrome 2019-10-09 criteria provided, single submitter clinical testing The c.80+1G>C intronic variant results from a G to C substitution one nucleotide after coding exon 1 of the BRCA1 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Similar alterations at this splice donor site through +5 have been shown to cause skipping of coding exon 1 (also known as Exon 2) with resulting loss of the start codon (Ambry internal data; Steffensen AY et al. Eur J Hum Genet. 2014 Dec;22(12):1362-8). One 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). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as disease-causing mutation.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111705 SCV000144208 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2004-11-25 no assertion criteria provided clinical testing
Brotman Baty Institute, University of Washington RCV000111705 SCV001243697 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro

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