2-208142738-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005210.4(CRYGB):c.428G>A(p.Arg143Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005210.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CRYGB | NM_005210.4 | c.428G>A | p.Arg143Lys | missense_variant | Exon 3 of 3 | ENST00000260988.5 | NP_005201.2 | |
CRYGB | XM_017003402.2 | c.434G>A | p.Arg145Lys | missense_variant | Exon 3 of 3 | XP_016858891.1 | ||
LOC100507443 | NR_038437.1 | n.221+5559C>T | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251410Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135878
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461880Hom.: 0 Cov.: 29 AF XY: 0.0000165 AC XY: 12AN XY: 727238
GnomAD4 genome AF: 0.000190 AC: 29AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74460
ClinVar
Submissions by phenotype
Cataract 39 multiple types Uncertain:1
This variant has not been reported in the literature in individuals affected with CRYGB-related conditions. 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. 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 tolerated. This variant is present in population databases (rs144172331, gnomAD 0.05%). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 143 of the CRYGB protein (p.Arg143Lys). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at