NM_201253.3:c.1183G>T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_201253.3(CRB1):c.1183G>T(p.Glu395*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000328 in 152,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E395E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_201253.3 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CRB1 | NM_201253.3 | c.1183G>T | p.Glu395* | stop_gained | Exon 6 of 12 | ENST00000367400.8 | NP_957705.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152152Hom.: 0 Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1437248Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 716742
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152270Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74448
ClinVar
Submissions by phenotype
Leber congenital amaurosis Pathogenic:1
- -
Leber congenital amaurosis 8 Pathogenic:1
- -
Retinitis pigmentosa 12;C3151202:Leber congenital amaurosis 8 Pathogenic:1
This sequence change creates a premature translational stop signal (p.Glu395*) in the CRB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CRB1 are known to be pathogenic (PMID: 10508521, 22065545, 23379534, 25412400, 26957898, 28041643, 29391521). This variant is present in population databases (rs369775002, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with Leber congenital amaurosis (PMID: 28041643). ClinVar contains an entry for this variant (Variation ID: 438069). For these reasons, this variant has been classified as Pathogenic. -
Retinal dystrophy Pathogenic:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at