Submissions for variant NM_007294.4(BRCA1):c.4683C>G (p.Thr1561=)

dbSNP: rs878853265

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000482214	SCV000568442	uncertain significance	not provided	2016-09-21	criteria provided, single submitter	clinical testing	This variant is denoted BRCA1 c.4683C>G at the DNA level. This variant is silent at the coding level, preserving a Threonine at codon 1561. Using alternate nomenclature, this variant would be defined as BRCA1 4802C>G. It is not predicted to cause abnormal splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. BRCA1 c.4683C>G was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The nucleotide which is altered, a cytosine (C) at base 4683, is conserved through mammals. Based on currently available information, it is unclear whether BRCA1 c.4683C>G is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae	RCV000559495	SCV000635992	likely benign	Hereditary breast ovarian cancer syndrome	2023-05-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002329148	SCV002634495	likely benign	Hereditary cancer-predisposing syndrome	2021-05-15	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.