4-47031697-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000812.4(GABRB1):c.46C>T(p.Pro16Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,006 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. P16H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000812.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRB1 | NM_000812.4 | c.46C>T | p.Pro16Ser | missense_variant | 1/9 | ENST00000295454.8 | |
GABRB1 | XM_017007986.3 | c.46C>T | p.Pro16Ser | missense_variant | 1/5 | ||
GABRB1 | XM_024453976.2 | c.-19-217C>T | intron_variant | ||||
GABRB1 | XM_024453977.2 | c.-19-217C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRB1 | ENST00000295454.8 | c.46C>T | p.Pro16Ser | missense_variant | 1/9 | 1 | NM_000812.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152006Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152006Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74248
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 21, 2023 | 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. 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. This variant has not been reported in the literature in individuals affected with GABRB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 16 of the GABRB1 protein (p.Pro16Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at