Variant 4-47031688-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000812.4(GABRB1):c.37C>T(p.Leu13Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GABRB1
NM_000812.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.799

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]

GABRB1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.121206135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GABRB1	NM_000812.4 linkuse as main transcript	c.37C>T	p.Leu13Phe	missense_variant	1/9	ENST00000295454.8	NP_000803.2
GABRB1	XM_017007986.3 linkuse as main transcript	c.37C>T	p.Leu13Phe	missense_variant	1/5		XP_016863475.1
GABRB1	XM_024453976.2 linkuse as main transcript	c.-19-226C>T		intron_variant			XP_024309744.1
GABRB1	XM_024453977.2 linkuse as main transcript	c.-19-226C>T		intron_variant			XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB1	ENST00000295454.8 linkuse as main transcript	c.37C>T	p.Leu13Phe	missense_variant	1/9	1	NM_000812.4	ENSP00000295454	P1	P18505-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251486

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135918

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727194

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 11, 2022

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 present in population databases (rs763566824, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 13 of the GABRB1 protein (p.Leu13Phe). 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.61

M_CAP

Benign

0.039

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.46

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.040

REVEL

Benign

0.24

Sift

Benign

0.45

Sift4G

Benign

0.68

Polyphen

0.0

Vest4

0.18

MutPred

0.43

Loss of helix (P = 0.079);

MVP

0.47

MPC

0.016

ClinPred

0.15

GERP RS

3.6

Varity_R

0.11

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over