chr16-57897913-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM5PP3
The NM_001297.5(CNGB1):c.2978G>A(p.Gly993Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000137 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. 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. G993V) has been classified as Pathogenic.
Frequency
Consequence
NM_001297.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNGB1 | NM_001297.5 | c.2978G>A | p.Gly993Glu | missense_variant, splice_region_variant | 30/33 | ENST00000251102.13 | |
CNGB1 | NM_001286130.2 | c.2960G>A | p.Gly987Glu | missense_variant, splice_region_variant | 30/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNGB1 | ENST00000251102.13 | c.2978G>A | p.Gly993Glu | missense_variant, splice_region_variant | 30/33 | 1 | NM_001297.5 | P4 | |
CNGB1 | ENST00000564448.5 | c.2960G>A | p.Gly987Glu | missense_variant, splice_region_variant | 30/33 | 1 | A2 | ||
CNGB1 | ENST00000565942.1 | c.26G>A | p.Gly9Glu | missense_variant, splice_region_variant | 2/4 | 5 | |||
CNGB1 | ENST00000569643.1 | n.635G>A | splice_region_variant, non_coding_transcript_exon_variant | 6/6 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 249556Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135398
GnomAD4 exome AF: 0.000145 AC: 212AN: 1461838Hom.: 0 Cov.: 32 AF XY: 0.000139 AC XY: 101AN XY: 727230
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 20, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 26, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 993 of the CNGB1 protein (p.Gly993Glu). This variant is present in population databases (rs121918532, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CNGB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 93702). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at