ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3416G>T (p.Ser1139Ile)

gnomAD frequency: 0.00001  dbSNP: rs80357228
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
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) RCV000112090 SCV001161584 benign Breast-ovarian cancer, familial, susceptibility to, 1 2019-06-18 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000012
Invitae RCV000048184 SCV000076197 likely benign Hereditary breast ovarian cancer syndrome 2023-12-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000132045 SCV000187105 likely benign Hereditary cancer-predisposing syndrome 2021-06-07 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Michigan Medical Genetics Laboratories, University of Michigan RCV000112090 SCV000195919 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2014-11-03 criteria provided, single submitter clinical testing
GeneDx RCV000235128 SCV000210146 likely benign not provided 2020-03-17 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20104584, 12938098, 23704879, 31131967, 16267036, 10923033)
Color Diagnostics, LLC DBA Color Health RCV000132045 SCV000902967 likely benign Hereditary cancer-predisposing syndrome 2016-02-22 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001194406 SCV002070149 uncertain significance not specified 2020-02-11 criteria provided, single submitter clinical testing DNA sequence analysis of the BRCA1 gene demonstrated a sequence change, c.3416G>T, in exon 10 that results in an amino acid change, p.Ser1139Ile. This sequence change does not appear to have been previously described in patients with BRCA1-related disorders and has been described in the gnomAD database in three individuals (dbSNP rs80357228). The p.Ser1139Ile change affects a moderately conserved amino acid residue located in a domain of the BRCA1 protein that is known to be functional. The p.Ser1139Ile substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to the lack of functional studies, the clinical significance of the p.Ser1139Ile change remains unknown at this time.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV001194406 SCV002551000 benign not specified 2023-08-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004554660 SCV004120319 uncertain significance BRCA1-related disorder 2023-08-05 criteria provided, single submitter clinical testing The BRCA1 c.3416G>T variant is predicted to result in the amino acid substitution p.Ser1139Ile. This variant was reported in at least one patient with breast cancer, however, no other information was available (for example, supple. Table 2 in Borg et al. 2010. PubMed ID: 20104584). Of note, this variant occurs within a region of the BRCA1 gene that is predicted to be tolerant to variation (Table 2, Dines et al. 2020. PubMed ID: 31911673). This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-41244132-C-A). This variant is classified as benign, or uncertain variant in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/54873/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235128 SCV004219354 uncertain significance not provided 2023-05-03 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000026 (3/113598 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals affected with breast and/or ovarian cancer (PMIDs: 12938098 (2003), 16267036 (2005), 20104584 (2010), and 33471991 (2021); LOVD3 Shared (https://databases.lovd.nl/shared/)). This variant was also reported in healthy cancer-free individuals (FLOSSIES, (https://whi.color.com/), PMID: 33471991 (2021); LOVD3 Shared (https://databases.lovd.nl/shared/)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112090 SCV000144756 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2004-11-25 no assertion criteria provided clinical testing
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency RCV000048184 SCV000586892 uncertain significance Hereditary breast ovarian cancer syndrome 2016-04-14 no assertion criteria provided clinical testing
BRCAlab, Lund University RCV000112090 SCV004244045 benign Breast-ovarian cancer, familial, susceptibility to, 1 2020-03-02 no assertion criteria provided 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.