rs369775002
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1
The NM_201253.3(CRB1):c.1183G>A(p.Glu395Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000201 in 1,589,402 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. E395E) has been classified as Likely benign.
Frequency
Consequence
NM_201253.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CRB1 | NM_201253.3 | c.1183G>A | p.Glu395Lys | missense_variant | Exon 6 of 12 | ENST00000367400.8 | NP_957705.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152152Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251228Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135788
GnomAD4 exome AF: 0.0000188 AC: 27AN: 1437250Hom.: 0 Cov.: 28 AF XY: 0.0000195 AC XY: 14AN XY: 716742
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152152Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74320
ClinVar
Submissions by phenotype
Retinitis pigmentosa 12;C3151202:Leber congenital amaurosis 8 Uncertain:1
This sequence change replaces glutamic acid with lysine at codon 395 of the CRB1 protein (p.Glu395Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs369775002, ExAC 0.01%). This variant has not been reported in the literature in individuals with CRB1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at