17-29250202-G-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PP3BS2
The NM_005208.5(CRYBA1):c.117G>C(p.Glu39Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000287 in 1,604,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_005208.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CRYBA1 | ENST00000225387.8 | c.117G>C | p.Glu39Asp | missense_variant | Exon 3 of 6 | 1 | NM_005208.5 | ENSP00000225387.3 | ||
CRYBA1 | ENST00000484605.1 | n.105G>C | non_coding_transcript_exon_variant | Exon 3 of 5 | 5 | ENSP00000464368.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251488Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135918
GnomAD4 exome AF: 0.0000282 AC: 41AN: 1452010Hom.: 0 Cov.: 29 AF XY: 0.0000290 AC XY: 21AN XY: 723116
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74338
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.117G>C (p.E39D) alteration is located in exon 3 (coding exon 3) of the CRYBA1 gene. This alteration results from a G to C substitution at nucleotide position 117, causing the glutamic acid (E) at amino acid position 39 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Cataract 10 multiple types Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 39 of the CRYBA1 protein (p.Glu39Asp). This variant is present in population databases (rs200145139, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CRYBA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2598608). 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 tolerated. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at