ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4245A>G (p.Glu1415=) (rs41293453)

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Total submissions: 10
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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) RCV000112303 SCV000578431 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/).
Invitae RCV000048499 SCV000076512 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000163656 SCV000214226 likely benign Hereditary cancer-predisposing syndrome 2014-11-20 criteria provided, single submitter clinical testing
GeneDx RCV000483384 SCV000564741 likely benign not specified 2017-12-06 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.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000483384 SCV000591500 likely benign not specified 2014-10-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586731 SCV000699124 likely benign not provided 2016-03-22 criteria provided, single submitter clinical testing Variant Summary: This BRCA1 variant results in no amino acid change, is located in exon 12 and >20 base-pairs away from the intron 11/exon 12 boundary, and involves a non-conserved nucleotide. MutationTaster predicts this variant to be disease-causing. However, 5/5 silico programs in Alamut predict this variant not to affect normal splicing. The variant was found in 4/121396 control chromosomes at a frequency of 0.000033, which does not significantly exceed maximal expected frequency of a pathogenic allele (0.0010005). Although the variant has been cited in breast/ovarian cancer patients in the literature, there have been no co-segregation studies for this variant, nor in vitro/vivo functional studies. One clinical diagnostic lab has classified the variant as likely benign, and 3/3 independent published studies have classified this variant as a 'polymorphism' without evidence to independently evaluate, including Judkins_2005 from Myriad Genetics Lab. Considering all currently available evidence, the variant is classified as Likely Benign.
Counsyl RCV000112303 SCV000785995 likely benign Breast-ovarian cancer, familial 1 2018-01-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586731 SCV000888914 likely benign not provided 2018-03-07 criteria provided, single submitter clinical testing
Color RCV000163656 SCV000902936 likely benign Hereditary cancer-predisposing syndrome 2015-08-03 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112303 SCV000145039 uncertain significance Breast-ovarian cancer, familial 1 2000-01-01 no assertion criteria provided clinical testing

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