ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.1474-3T>C

gnomAD frequency: 0.00001  dbSNP: rs552752779
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164980 SCV000215673 likely benign Hereditary cancer-predisposing syndrome 2020-08-31 criteria provided, single submitter clinical testing RNA Studies
Invitae RCV001085989 SCV000255149 likely benign Familial cancer of breast; Fanconi anemia complementation group J 2021-11-23 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV000348888 SCV000404610 uncertain significance Fanconi anemia complementation group J 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000430204 SCV000512417 benign not specified 2015-09-21 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.
Genetic Services Laboratory,University of Chicago RCV000430204 SCV000593766 uncertain significance not specified 2016-12-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589721 SCV000699667 benign not provided 2017-05-08 criteria provided, single submitter clinical testing Variant summary: The BRIP1 c.1474-3T>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing, though ESE finder predicts the variant may introduce an SF2/ASF ESE site at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC in 33 of 120864 control chromosomes from all ethnicities, but was predominantly observed in the South Asian subpopulation at a frequency of 0.001879 (31/16496). This frequency is about 30 times the estimated maximal expected allele frequency of a pathogenic BRIP1 variant (0.0000625), strongly suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. Multiple clinical diagnostic laboratories have conflicting classifications for this variant including uncertain significance (4x in ClinVar) and benign (1x in ClinVar). The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Counsyl RCV000662494 SCV000785013 uncertain significance Fanconi anemia complementation group J; Neoplasm of ovary 2017-03-14 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000164980 SCV000902752 benign Hereditary cancer-predisposing syndrome 2016-11-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589721 SCV002046872 benign not provided 2021-04-07 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000164980 SCV002531358 likely benign Hereditary cancer-predisposing syndrome 2021-04-13 criteria provided, single submitter curation
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000348888 SCV001550572 uncertain significance Fanconi anemia complementation group J no assertion criteria provided clinical testing The BRIP1 c.1474-3T>C variant was not identified in the literature nor was it identified in the Cosmic or Zhejiang University Database. The variant was identified in dbSNP (ID: rs552752779) “With Uncertain significance allele”, ClinVar (with conflicting interpretations of pathogenicity; submitters: benign by GeneDx and uncertain significance by Ambry Genetics, Invitae, Illumina Clinical Services Laboratory and Genetic Services Laboratory-University of Chicago), Clinvitae (4x), and in control databases in 51 (1 homozygous) of 246022 chromosomes at a frequency of 0.0002 (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations: European Non-Finnish in 1 of 111556 chromosomes (frequency: 0.000009) and South Asian in 50 (1 homozygous) of 30762 chromosomes (frequency: 0.002). The c.1474-3T>C variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions; however, position -3 is part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as uncertain significance.

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.