Variant 5-161685998-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The ENST00000274545.10(GABRA6):c.9G>A(p.Ser3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,611,882 control chromosomes in the GnomAD database, including 46,739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 3113 hom., cov: 32)

Exomes 𝑓: 0.24 ( 43626 hom. )

Consequence

GABRA6
ENST00000274545.10 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.855

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 5-161685998-G-A is Benign according to our data. Variant chr5-161685998-G-A is described in ClinVar as [Benign]. Clinvar id is 1169909.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.855 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA6	NM_000811.3 linkuse as main transcript	c.9G>A	p.Ser3=	synonymous_variant	1/9	ENST00000274545.10	NP_000802.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GABRA6	ENST00000274545.10 linkuse as main transcript	c.9G>A	p.Ser3=	synonymous_variant	1/9	1	NM_000811.3	ENSP00000274545	P1
GABRA6	ENST00000523217.5 linkuse as main transcript	c.9G>A	p.Ser3=	synonymous_variant	1/9	5		ENSP00000430527
GABRA6	ENST00000522269.5 linkuse as main transcript	n.352-232G>A		intron_variant, non_coding_transcript_variant		4
GABRA6	ENST00000518888.1 linkuse as main transcript			downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26950

AN:

152006

Hom.:

3113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0462

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.284

Gnomad EAS

AF:

0.0739

Gnomad SAS

AF:

0.0847

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.173

GnomAD3 exomes

AF:

0.190

AC:

47863

AN:

251412

Hom.:

5443

AF XY:

0.192

AC XY:

26113

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.0429

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.295

Gnomad EAS exome

AF:

0.0755

Gnomad SAS exome

AF:

0.0892

Gnomad FIN exome

AF:

0.266

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.235

AC:

343052

AN:

1459758

Hom.:

43626

Cov.:

AF XY:

0.232

AC XY:

168206

AN XY:

726248

show subpopulations

Gnomad4 AFR exome

AF:

0.0414

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.294

Gnomad4 EAS exome

AF:

0.0672

Gnomad4 SAS exome

AF:

0.0901

Gnomad4 FIN exome

AF:

0.264

Gnomad4 NFE exome

AF:

0.261

Gnomad4 OTH exome

AF:

0.224

GnomAD4 genome

AF:

0.177

AC:

26949

AN:

152124

Hom.:

3113

Cov.:

AF XY:

0.175

AC XY:

12980

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0461

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.284

Gnomad4 EAS

AF:

0.0740

Gnomad4 SAS

AF:

0.0850

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.256

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.234

Hom.:

5962

Bravo

AF:

0.163

Asia WGS

AF:

0.0690

AC:

241

AN:

3478

EpiCase

AF:

0.248

EpiControl

AF:

0.247

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Childhood absence epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 13, 2023

- -

GABRA6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.7

DANN

Benign

0.77

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.

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