rs574162883
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_201253.3(CRB1):c.2839G>A(p.Glu947Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E947Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_201253.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRB1 | NM_201253.3 | c.2839G>A | p.Glu947Lys | missense_variant | 8/12 | ENST00000367400.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRB1 | ENST00000367400.8 | c.2839G>A | p.Glu947Lys | missense_variant | 8/12 | 1 | NM_201253.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000836 AC: 21AN: 251092Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135718
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461618Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28AN XY: 727110
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74456
ClinVar
Submissions by phenotype
Retinitis pigmentosa Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Retinitis pigmentosa 12;C1868310:Pigmented paravenous retinochoroidal atrophy;C3151202:Leber congenital amaurosis 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 05, 2022 | - - |
Leber congenital amaurosis Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 15, 2020 | - - |
Leber congenital amaurosis 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Retinitis pigmentosa 12;C3151202:Leber congenital amaurosis 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 947 of the CRB1 protein (p.Glu947Lys). This variant is present in population databases (rs574162883, gnomAD 0.06%). This missense change has been observed in individuals with autosomal recessive retinitis pigmentosa (PMID: 28041643, 32581362). ClinVar contains an entry for this variant (Variation ID: 438077). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CRB1 protein function. 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. - |
Retinitis pigmentosa 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Pigmented paravenous retinochoroidal atrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at