Submissions for variant NM_001114753.3(ENG):c.1429-8C>T

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003078409	SCV003474539	likely benign	Hereditary hemorrhagic telangiectasia	2022-10-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003994495	SCV004813195	likely benign	not specified	2024-02-20	criteria provided, single submitter	clinical testing	Variant summary: ENG c.1429-8C>T alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 7.5e-06 in 1606044 control chromosomes, predominantly at a frequency of 0.00012 within the African or African-American subpopulation in the gnomAD database (v4.0 dataset). This frequency is higher than the estimated maximum expected for a pathogenic variant in ENG causing Hereditary Hemorrhagic Telangiectasia (4.2e-05), suggesting that this variant is likely not associated with a highly penetrant, early onset dominant disease. To our knowledge, no occurrence of c.1429-8C>T in individuals affected with Hereditary Hemorrhagic Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2161109). Based on the evidence outlined above, the variant was classified as likely benign.