ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.75C>T (p.Pro25=) (rs80356839)

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Total submissions: 11
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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) RCV000111695 SCV000578460 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;
Invitae RCV001080723 SCV000077135 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000163150 SCV000213667 likely benign Hereditary cancer-predisposing syndrome 2014-08-04 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.
Baylor Genetics RCV000469236 SCV000540981 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000496708 SCV000586861 benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Department of Pathology and Molecular Medicine,Queen's University RCV000496708 SCV000588023 benign not specified 2017-04-20 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000755220 SCV000602696 benign not provided 2017-05-24 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163150 SCV000683354 likely benign Hereditary cancer-predisposing syndrome 2015-04-13 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000111695 SCV000144197 benign Breast-ovarian cancer, familial 1 2006-07-19 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353769 SCV000591233 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 p.Pro25Pro variant was identified in the literature (Bowles_2014_Myriad Publ, Ozcelik H_2012_22874498). However, no proband information was available. The variant was identified in dbSNP (ID: rs80356839) “With Likely benign allele”, Exome Aggregation Consortium (ExAC) database (released Oct 20th, 2014) in 4 of 120942 chromosomes (frequency: 3.31e-05) from a population of East Asian (4 of 8640 chromosomes) The variant was not found in African, Latino, South Asian, European (Finnish), European (Non-Finnish) and other individuals. The variant was also identified in the ClinVar database (classified as a Benign by BIC and Gene DX and as Likely Benign by Invitae), GeneInsight through the Canadian Open Genetics Repository ( (2X, classified as “IARC1 and IARC2” by 2 clinical laboratories), the BIC database (1X with unknown clinical importance).The variant was also previously identified by our laboratory 6X.The Pro25Pro variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. Additionally, at the ACMG Meeting in March 2014, ( Bowles_2014_Myriad Publ) Myriad announced that “BRCA1 c.75C>T (p.Pro25Pro) has been previously observed in a patient with decreased mRNA transcript levels and was postulated to be pathogenic. However, in Myriad’s patient population, this variant co-occurs in trans with known deleterious BRCA1 mutations in five patients and has been found in the homozygous state in 14 patients, strongly indicating a benign classification. History weighting analysis confirms the benign nature of this variant.” In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
King Laboratory,University of Washington RCV000496708 SCV001251288 benign not specified 2019-09-01 no assertion criteria provided research

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