ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.528G>A (p.Thr176=) (rs34545365)

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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) RCV000495208 SCV000578204 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 RCV000123882 SCV000167227 benign not specified 2013-11-04 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 RCV000163742 SCV000214318 likely benign Hereditary cancer-predisposing syndrome 2014-09-18 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001080170 SCV000253513 benign Hereditary breast and ovarian cancer syndrome 2020-12-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000123882 SCV000605914 likely benign not specified 2016-12-08 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163742 SCV000683283 likely benign Hereditary cancer-predisposing syndrome 2016-01-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000123882 SCV000699233 likely benign not specified 2019-08-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586657 SCV000887717 benign not provided 2018-06-19 criteria provided, single submitter clinical testing
Mendelics RCV000495208 SCV001140632 likely benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353437 SCV000591277 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The p.Thr176Thr variant has been identified in two cases were identified in the UMD database and they were reported as unclassified variant. It is also listed in the dbSNP database (ID#: rs34545365) an infrequent variant with an average heterozygosity of 0.002+/-0.032, and increasing the likelihood that this variant is benign. This variant is not expected to have clinical significance because it does not alter an amino acid residue, and occurs outside of the splicing consensus sequence. In-silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict change at the splice site, however this information is not very predictive of pathogenicity. In summary, we cannot rule out that this variant may contribute to or modify the clinical features observed in this individual, but based on the above information, this variant is classified as predicted benign.

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