ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.671-6T>G (rs878854964)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230230 SCV000289838 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-02-24 criteria provided, single submitter clinical testing This sequence change falls in intron 9 of the BRCA1 mRNA. It does not directly change the encoded amino acid sequence of the BRCA1 protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a novel intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000503426 SCV000591293 uncertain significance not specified 2012-06-29 criteria provided, single submitter clinical testing
Color RCV001183555 SCV001349334 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000503426 SCV001363879 uncertain significance not specified 2019-02-19 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.671-6T>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict an impact on normal splicing: Four predict the variant weakens a 3 acceptor site. One predict the variant abolishes a 3 acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 254334 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.671-6T>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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