Submissions for variant NM_201253.3(CRB1):c.4005+1G>A

dbSNP: rs890453675

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome-Nilou Lab	RCV001250622	SCV001810377	pathogenic	Leber congenital amaurosis 8	2021-07-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002549197	SCV003524000	pathogenic	Retinitis pigmentosa 12; Leber congenital amaurosis 8	2023-10-07	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 11 of the CRB1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (no rsID available, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with clinical features of CRB1-related conditions (PMID: 15024725, 20683928, 23379534, 31456290). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 812303). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV001250622	SCV004211217	pathogenic	Leber congenital amaurosis 8	2023-12-14	criteria provided, single submitter	clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001003000	SCV001161054	pathogenic	Leber congenital amaurosis	2019-06-23	no assertion criteria provided	research
Laboratory of Genetics in Ophthalmology, Institut Imagine	RCV001250622	SCV001425492	pathogenic	Leber congenital amaurosis 8		no assertion criteria provided	research