chr22-26599551-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_001887.4(CRYBB1):c.698G>A(p.Arg233His) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R233C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001887.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYBB1 | NM_001887.4 | c.698G>A | p.Arg233His | missense_variant | 6/6 | ENST00000647684.1 | |
CRYBB1 | XM_011529899.4 | c.698G>A | p.Arg233His | missense_variant | 6/6 | ||
CRYBA4 | XM_006724140.4 | c.-239+2468C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYBB1 | ENST00000647684.1 | c.698G>A | p.Arg233His | missense_variant | 6/6 | NM_001887.4 | P1 | ||
ENST00000668614.1 | n.56+2468C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251188Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135828
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461768Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727198
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152246Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74390
ClinVar
Submissions by phenotype
Cataract 17 multiple types Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 02, 2023 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects CRYBB1 function (PMID: 25086334). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This missense change has been observed in individual(s) with congenital cataract (PMID: 21402992). In at least one individual the variant was observed to be de novo. This variant is present in population databases (rs575368335, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 233 of the CRYBB1 protein (p.Arg233His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at