ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3747C>T (p.Thr1249=) (rs587780801)

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
Ambry Genetics RCV000162653 SCV000213091 likely benign Hereditary cancer-predisposing syndrome 2015-05-08 criteria provided, single submitter clinical testing
Color RCV000162653 SCV000537491 likely benign Hereditary cancer-predisposing syndrome 2015-08-04 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000495200 SCV000744628 likely benign Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495200 SCV000578201 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 RCV000437653 SCV000517873 likely benign not specified 2016-10-03 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.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000495200 SCV000743402 likely benign Breast-ovarian cancer, familial 1 2017-07-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586631 SCV000699067 uncertain significance not provided 2016-03-18 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3747C>T affects a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a benign outcome. 5/5 in silico programs via Alamut predict no significant change on the RNA splicing sites, while SEfinder predicts changes of binding motifs for RNA splicing enhancers. However, it has been reported that this variant does not dramatically affect splicing when evaluated via minigene assay (Anczukow_Genes Chromosomes and Cancer_2008; data not shown). This variant was found in 5/121390 control chromosomes at a frequency of 0.0000412, which does not significantly exceed maximal expected frequency of a pathogenic allele (0.0010005). This variant has been reported in multiple affected individuals without strong evidence for causality (i.e. co-segregation data). In addition, two clinical laboratories via ClinVar classified this variant as likely benign without evidence to independently evaluate. The variant has not been reported to co-occur with other pathogenic variants. Taken together, this variant was classified as a VUS-possibly benign until more information becomes available.
Invitae RCV000123273 SCV000166580 likely benign Hereditary breast and ovarian cancer syndrome 2017-11-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586631 SCV000888895 likely benign not provided 2018-03-07 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.