chr4-47031685-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_000812.4(GABRB1):c.34C>T(p.Leu12Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,610,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000812.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GABRB1 | NM_000812.4 | c.34C>T | p.Leu12Phe | missense_variant | 1/9 | ENST00000295454.8 | NP_000803.2 | |
GABRB1 | XM_017007986.3 | c.34C>T | p.Leu12Phe | missense_variant | 1/5 | XP_016863475.1 | ||
GABRB1 | XM_024453976.2 | c.-19-229C>T | intron_variant | XP_024309744.1 | ||||
GABRB1 | XM_024453977.2 | c.-19-229C>T | intron_variant | XP_024309745.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GABRB1 | ENST00000295454.8 | c.34C>T | p.Leu12Phe | missense_variant | 1/9 | 1 | NM_000812.4 | ENSP00000295454 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251486Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135914
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1458530Hom.: 0 Cov.: 30 AF XY: 0.00000965 AC XY: 7AN XY: 725738
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 19, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 12 of the GABRB1 protein (p.Leu12Phe). This variant is present in population databases (rs199819422, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with GABRB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1946972). 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 GABRB1 protein function with a negative predictive value of 95%. 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