ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5153-3T>C (rs375639469)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165729 SCV000216470 uncertain significance Hereditary cancer-predisposing syndrome 2014-08-28 criteria provided, single submitter clinical testing
Invitae RCV000474546 SCV000549402 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-11-11 criteria provided, single submitter clinical testing This sequence change falls in intron 17 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs375639469, ExAC 0.01%). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 91639). Nucleotide substitutions within 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 is not likely to affect RNA splicing, 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.
Integrated Genetics/Laboratory Corporation of America RCV000588488 SCV000699214 uncertain significance not provided 2017-01-03 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.5153-3T>C variant involves the alteration of a non-conserved intronic nucleotide, which 5/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/119938, which does not exceed the estimated maximal expected allele frequency for a pathogenic BRCA1 variant of 1/1000. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, although multiple clinical diagnostic laboratories classify the variant as "uncertain significance." Therefore, until additional information becomes available (ie, clinical and/or functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)."
GeneDx RCV000616210 SCV000730671 likely benign not specified 2017-07-28 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.
Color RCV000165729 SCV000912006 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-30 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077156 SCV000108953 uncertain significance Breast-ovarian cancer, familial 1 2009-10-13 no assertion criteria provided clinical testing

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