Submissions for variant NM_001032221.6(STXBP1):c.903-4C>G

gnomAD frequency: 0.00016  dbSNP: rs369625158

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000420337	SCV000514813	benign	not specified	2015-07-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genetic Services Laboratory, University of Chicago	RCV000420337	SCV000597311	likely benign	not specified	2015-11-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000556322	SCV000633907	likely benign	Early infantile epileptic encephalopathy with suppression bursts	2024-11-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000420337	SCV005886305	benign	not specified	2025-02-06	criteria provided, single submitter	clinical testing	Variant summary: STXBP1 c.903-4C>G alters a non-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 0.00011 in 1613892 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in STXBP1 causing Developmental And Epileptic Encephalopathy, 4, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.903-4C>G in individuals affected with Developmental And Epileptic Encephalopathy, 4 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 378688). Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV005411426	SCV006077858	likely benign	not provided	2025-04-01	criteria provided, single submitter	clinical testing	STXBP1: BP4
PreventionGenetics, part of Exact Sciences	RCV004551430	SCV004750501	likely benign	STXBP1-related disorder	2019-06-25	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).