ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.3559G>A (p.Ala1187Thr) (rs367610893)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573454 SCV000661468 uncertain significance Hereditary cancer-predisposing syndrome 2017-04-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Color RCV000573454 SCV000911224 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-25 criteria provided, single submitter clinical testing
Counsyl RCV000662546 SCV000785128 uncertain significance Fanconi anemia, complementation group J; Neoplasm of ovary 2017-05-01 criteria provided, single submitter clinical testing
GeneDx RCV000160327 SCV000210830 uncertain significance not provided 2018-12-07 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.3559G>A at the cDNA level, p.Ala1187Thr (A1187T) at the protein level, and results in the change of an Alanine to a Threonine (GCT>ACT). This variant has been reported in at least one individual with breast cancer (Easton 2016). BRIP1 Ala1187Thr was observed at an allele frequency of 0.05% (13/24002) in individuals of African ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRIP1 Ala1187Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000226626 SCV000291043 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1187 of the BRIP1 protein (p.Ala1187Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs367610893, ExAC 0.05%). This variant has been reported in an individual affected with breast cancer (PMID: 26921362). ClinVar contains an entry for this variant (Variation ID: 182337). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000709523 SCV000839347 uncertain significance Fanconi anemia, complementation group J 2018-07-02 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.