rs1057520152
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_201253.3(CRB1):βc.3988delβ(p.Glu1330SerfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. E1330E) has been classified as Likely benign.
Frequency
Consequence
NM_201253.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRB1 | NM_201253.3 | c.3988del | p.Glu1330SerfsTer11 | frameshift_variant | 11/12 | ENST00000367400.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRB1 | ENST00000367400.8 | c.3988del | p.Glu1330SerfsTer11 | frameshift_variant | 11/12 | 1 | NM_201253.3 | P1 | |
ENST00000422250.1 | n.259del | non_coding_transcript_exon_variant | 2/4 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727242
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Leber congenital amaurosis 8 Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 17, 2023 | - - |
Pathogenic, no assertion criteria provided | research | Laboratory of Genetics in Ophthalmology, Institut Imagine | - | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not provided Pathogenic:3
Likely pathogenic, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 28, 2016 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Leber congenital amaurosis Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Retinitis pigmentosa 12;C3151202:Leber congenital amaurosis 8 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | This sequence change creates a premature translational stop signal (p.Glu1330Serfs*11) in the CRB1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 77 amino acid(s) of the CRB1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Leber congenital amaurosis (PMID: 15024725). ClinVar contains an entry for this variant (Variation ID: 377183). This variant disrupts a region of the CRB1 protein in which other variant(s) (p.Arg1390*) have been determined to be pathogenic (PMID: 23379534, 24715753, 29068479). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Retinitis pigmentosa 12 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Retinal dystrophy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Jan 15, 2019 | - - |
Pigmented paravenous retinochoroidal atrophy Pathogenic:1
Likely pathogenic, 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