rs76962261
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_000814.6(GABRB3):c.1269C>G(p.His423Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000814.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000139 AC: 35AN: 251380Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135870
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727244
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74338
ClinVar
Submissions by phenotype
Epilepsy, childhood absence, susceptibility to, 5;C4310712:Developmental and epileptic encephalopathy, 43 Benign:1
This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.04% (7/15278) (https://gnomad.broadinstitute.org/variant/15-26547946-G-C?dataset=gnomad_r3). This variant is present in ClinVar, with multiple labs classifying this variant as Likely benign or Benign (Variation ID:409960). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign. -
GABRB3-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Epilepsy, childhood absence, susceptibility to, 1;C2677087:Epilepsy, childhood absence, susceptibility to, 5 Benign:1
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not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at