Variant 5-161692119-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000811.3(GABRA6):c.1005C>G(p.Ala335=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,613,736 control chromosomes in the GnomAD database, including 236,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.48 ( 18132 hom., cov: 33)

Exomes 𝑓: 0.54 ( 218775 hom. )

Consequence

GABRA6
NM_000811.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.318

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 5-161692119-C-G is Benign according to our data. Variant chr5-161692119-C-G is described in ClinVar as [Benign]. Clinvar id is 1169911.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.318 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 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.1005C>G	p.Ala335=	synonymous_variant	8/9	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.1005C>G	p.Ala335=	synonymous_variant	8/9	1	NM_000811.3	ENSP00000274545	P1
GABRA6	ENST00000523217.5 linkuse as main transcript	c.975C>G	p.Ala325=	synonymous_variant	8/9	5		ENSP00000430527
GABRA6	ENST00000521520.1 linkuse as main transcript	n.998C>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72734

AN:

151912

Hom.:

18131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.361

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.526

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.553

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.454

GnomAD3 exomes

AF:

0.481

AC:

121057

AN:

251464

Hom.:

30595

AF XY:

0.488

AC XY:

66374

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.360

Gnomad AMR exome

AF:

0.343

Gnomad ASJ exome

AF:

0.533

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.542

Gnomad NFE exome

AF:

0.565

Gnomad OTH exome

AF:

0.506

GnomAD4 exome

AF:

0.542

AC:

792173

AN:

1461706

Hom.:

218775

Cov.:

AF XY:

0.540

AC XY:

392925

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.362

Gnomad4 AMR exome

AF:

0.351

Gnomad4 ASJ exome

AF:

0.535

Gnomad4 EAS exome

AF:

0.311

Gnomad4 SAS exome

AF:

0.448

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.572

Gnomad4 OTH exome

AF:

0.522

GnomAD4 genome

AF:

0.478

AC:

72744

AN:

152030

Hom.:

18132

Cov.:

AF XY:

0.476

AC XY:

35390

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.360

Gnomad4 AMR

AF:

0.427

Gnomad4 ASJ

AF:

0.526

Gnomad4 EAS

AF:

0.304

Gnomad4 SAS

AF:

0.430

Gnomad4 FIN

AF:

0.553

Gnomad4 NFE

AF:

0.567

Gnomad4 OTH

AF:

0.450

Alfa

AF:

0.457

Hom.:

2405

Bravo

AF:

0.460

Asia WGS

AF:

0.342

AC:

1191

AN:

3478

EpiCase

AF:

0.559

EpiControl

AF:

0.554

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 16, 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

-0.76

CADD

Benign

7.1

DANN

Benign

0.55

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