ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5175A>G (p.Glu1725=) (rs191373374)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000410590 SCV000578251 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 RCV000123933 SCV000167320 benign not specified 2014-03-27 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.
Ambry Genetics RCV000163992 SCV000214593 likely benign Hereditary cancer-predisposing syndrome 2014-12-18 criteria provided, single submitter clinical testing
Invitae RCV000588977 SCV000262479 benign not provided 2019-03-01 criteria provided, single submitter clinical testing
Counsyl RCV000410590 SCV000488591 likely benign Breast-ovarian cancer, familial 1 2016-05-03 criteria provided, single submitter clinical testing
Color RCV000163992 SCV000683268 benign Hereditary cancer-predisposing syndrome 2015-12-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588977 SCV000699217 likely benign not provided 2017-03-17 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.5175A>G (p.Glu1725Glu) variant involves the alteration of a conserved nucleotide causing a synonymous change, which 5/5 splice prediction tools predict no significant impact on normal splicing or ESE binding. A functional study, Quiles_2016, support these predictions. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 4/120394 (1/30120), which does not exceed the estimated maximal expected allele frequency for a pathogenic BRCA1 variant of 1/1000. Multiple publications have cited the variant in affected individuals, although with limited information (ie, no co-occurrence and cosegregation data). A reputable database cites the variant in 14 individuals with a classification of "likely neutral," with 3 of the individuals carrying another pathogenic BRCA variant, 1 BRCA1, c.3839_3843delinsAGGC (p.Ser1280X) and 2 BRCA2s, c.1310_1313delAAGA (p.Lys437IlefsX22) and c.7234insG (p.Thr2412AspfsX2). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Therefore, taking all availble lines of evidence into consideration, the variant of interest has been classified as "likely benign."
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588977 SCV000888939 benign not provided 2019-07-17 criteria provided, single submitter clinical testing
Mendelics RCV000410590 SCV001140480 likely benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.