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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

GABRB1
NM_000812.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27293524).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GABRB1NM_000812.4 linkuse as main transcriptc.46C>T p.Pro16Ser missense_variant 1/9 ENST00000295454.8 NP_000803.2
GABRB1XM_017007986.3 linkuse as main transcriptc.46C>T p.Pro16Ser missense_variant 1/5 XP_016863475.1
GABRB1XM_024453976.2 linkuse as main transcriptc.-19-217C>T intron_variant XP_024309744.1
GABRB1XM_024453977.2 linkuse as main transcriptc.-19-217C>T intron_variant XP_024309745.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GABRB1ENST00000295454.8 linkuse as main transcriptc.46C>T p.Pro16Ser missense_variant 1/91 NM_000812.4 ENSP00000295454 P1P18505-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152006
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152006
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74248
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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), LabcorpMar 21, 2023In 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.021
T
Eigen
Benign
0.088
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.057
D
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.52
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
0.97
D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.1
N
REVEL
Uncertain
0.45
Sift
Benign
0.17
T
Sift4G
Benign
0.92
T
Polyphen
0.95
P
Vest4
0.21
MutPred
0.51
Loss of stability (P = 0.1152);
MVP
0.64
MPC
0.016
ClinPred
0.81
D
GERP RS
4.5
Varity_R
0.12
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs781754818; hg19: chr4-47033714; COSMIC: COSV54989451; API