5-161294209-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001371727.1(GABRB2):c.1411G>A(p.Ala471Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A471S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001371727.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRB2 | NM_001371727.1 | c.1411G>A | p.Ala471Thr | missense_variant | 10/10 | ENST00000393959.6 | |
GABRB2 | NM_021911.3 | c.1411G>A | p.Ala471Thr | missense_variant | 11/11 | ||
GABRB2 | NM_000813.3 | c.1297G>A | p.Ala433Thr | missense_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRB2 | ENST00000393959.6 | c.1411G>A | p.Ala471Thr | missense_variant | 10/10 | 1 | NM_001371727.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251356Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135844
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461840Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 727226
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Intellectual disability Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 23, 2022 | ClinVar contains an entry for this variant (Variation ID: 968953). This variant has not been reported in the literature in individuals affected with GABRB2-related conditions. This variant is present in population databases (rs140153076, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 471 of the GABRB2 protein (p.Ala471Thr). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GABRB2 protein function. 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