Variant rs76773579 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000811.3(GABRA6):c.710A>G(p.Gln237Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,613,782 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 10 hom. )

Consequence

GABRA6
NM_000811.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.41

Variant links:

Genes affected

GABRA6 (HGNC:4080): (gamma-aminobutyric acid type A receptor subunit alpha6) GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified. [provided by RefSeq, Jul 2008]

GABRA6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022625834).

BP6

Variant 5-161690237-A-G is Benign according to our data. Variant chr5-161690237-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 477869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA6	NM_000811.3 link	c.710A>G	p.Gln237Arg	missense_variant	7/9	ENST00000274545.10	NP_000802.2	Q16445

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA6	ENST00000274545.10 link	c.710A>G	p.Gln237Arg	missense_variant	7/9	1	NM_000811.3	ENSP00000274545.5		Q16445

Frequencies

GnomAD3 genomes

AF:

0.00227

AC:

345

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00366

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00309

AC:

776

AN:

251374

Hom.:

AF XY:

0.00324

AC XY:

440

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00418

Gnomad FIN exome

AF:

0.00513

Gnomad NFE exome

AF:

0.00384

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00291

AC:

4246

AN:

1461472

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

2226

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00356

Gnomad4 FIN exome

AF:

0.00530

Gnomad4 NFE exome

AF:

0.00303

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.00227

AC:

345

AN:

152310

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00386

Gnomad4 NFE

AF:

0.00366

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00317

Hom.:

Bravo

AF:

0.00197

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.00330

AC:

400

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00326

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Childhood absence epilepsy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 28, 2020

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

GABRA6-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 17, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

T;.;.;.

Eigen

Benign

-0.072

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.57

T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.023

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.16

N;.;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.090

N;N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.17

T;T;T;T

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.041

B;.;.;.

Vest4

0.44

MVP

0.78

MPC

0.43

ClinPred

0.024

GERP RS

5.3

Varity_R

0.26

gMVP

0.74

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.

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