4-47031677-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_000812.4(GABRB1):ā€‹c.26G>Cā€‹(p.Ser9Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

GABRB1
NM_000812.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05
Variant links:
Genes affected
GABRB1 (HGNC:4081): (gamma-aminobutyric acid type A receptor subunit beta1) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 1 subunit. It is mapped to chromosome 4p12 in a cluster comprised of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13778129).
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GABRB1NM_000812.4 linkuse as main transcriptc.26G>C p.Ser9Thr missense_variant 1/9 ENST00000295454.8 NP_000803.2
GABRB1XM_017007986.3 linkuse as main transcriptc.26G>C p.Ser9Thr missense_variant 1/5 XP_016863475.1
GABRB1XM_024453976.2 linkuse as main transcriptc.-19-237G>C intron_variant XP_024309744.1
GABRB1XM_024453977.2 linkuse as main transcriptc.-19-237G>C intron_variant XP_024309745.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GABRB1ENST00000295454.8 linkuse as main transcriptc.26G>C p.Ser9Thr missense_variant 1/91 NM_000812.4 ENSP00000295454 P1P18505-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251486
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461504
Hom.:
0
Cov.:
29
AF XY:
0.00000688
AC XY:
5
AN XY:
727060
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.000111
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 27, 2022In 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with GABRB1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 9 of the GABRB1 protein (p.Ser9Thr). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.053
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
20
DANN
Benign
0.87
DEOGEN2
Benign
0.017
T
Eigen
Benign
-0.071
Eigen_PC
Benign
0.041
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.59
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.030
N
REVEL
Benign
0.25
Sift
Benign
0.34
T
Sift4G
Benign
0.39
T
Polyphen
0.010
B
Vest4
0.15
MutPred
0.41
Gain of sheet (P = 0.0477);
MVP
0.73
MPC
0.017
ClinPred
0.57
D
GERP RS
4.5
Varity_R
0.11
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs764743206; hg19: chr4-47033694; API