ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.420T>C (p.Ser140=) (rs730881448)

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Total submissions: 7
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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) RCV000495624 SCV000578265 likely benign Breast-ovarian cancer, familial 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
GeneDx RCV000159860 SCV000209907 benign not specified 2014-09-15 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 RCV000464663 SCV000560250 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-29 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000159860 SCV000593664 likely benign not specified 2016-12-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV000568214 SCV000665422 likely benign Hereditary cancer-predisposing syndrome 2017-04-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign,In silico models in agreement (benign)
Color RCV000568214 SCV000683162 likely benign Hereditary cancer-predisposing syndrome 2017-06-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589069 SCV000699120 uncertain significance not provided 2017-04-04 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.420T>C (p.Ser140Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1/121398 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). One clinical diagnostic laboratory classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as VUS-possibly benign.

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