Submissions for variant NM_022168.4(IFIH1):c.1525-11C>A

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002889263	SCV003232033	likely benign	Singleton-Merten syndrome 1; Aicardi-Goutieres syndrome 7	2024-01-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004526945	SCV005040319	uncertain significance	not specified	2024-03-14	criteria provided, single submitter	clinical testing	Variant summary: IFIH1 c.1525-11C>A alters a conserved nucleotide located at a position not widely known to affect splicing. Several computational tools predict a significant impact on normal splicing: One predict the variant abolishes a 3' acceptor site. Two predict the variant weakens a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.7e-05 in 237846 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1525-11C>A in individuals affected with Aicardi-Goutieres Syndrome 7 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2026599). Based on the evidence outlined above, the variant was classified as uncertain significance.