ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.-19-3A>G (rs273898669)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000111498 SCV001161492 benign Breast-ovarian cancer, familial 1 2019-06-18 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000864
Counsyl RCV000111498 SCV000489261 uncertain significance Breast-ovarian cancer, familial 1 2016-09-13 criteria provided, single submitter clinical testing
GeneDx RCV000430917 SCV000516132 benign not specified 2015-09-01 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000867026 SCV001008210 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000111498 SCV001287539 uncertain significance Breast-ovarian cancer, familial 1 2017-04-27 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.
Breast Cancer Information Core (BIC) (BRCA1) RCV000111498 SCV000143940 uncertain significance Breast-ovarian cancer, familial 1 2010-09-18 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353407 SCV000591228 uncertain significance Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 c.-19-3A>G variant was not identified in the literature but was identified 2X in the BIC database as a variant of unknown clinical importance. This variant is located in the 3’ splice region of the BRCA1 5' untranslated region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In-silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predicts a greater than 10% difference in splicing in 3 of 5 different programs, with the creation of a splice acceptor site 2 nucleotides upstream from the known splice acceptor site. The c.-19-3A>G variant is located in a region that may be involved in promoter or splicing activity, thus this variant may affect the binding of transcription factors and processing or expression of the BRCA1 mRNA transcript; however there is no supporting data for this claim. In summary, the clinical significance of this variant cannot be determined with certainty at this time. Therefore this variant is a variant of unknown significance.
Brotman Baty Institute,University of Washington RCV000111498 SCV001242112 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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