Variant chr5-161689666-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000274545.10(GABRA6):c.560C>T(p.Thr187Met) variant causes a missense change. The variant allele was found at a frequency of 0.0136 in 1,608,520 control chromosomes in the GnomAD database, including 278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. T187T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.010 ( 10 hom., cov: 32)

Exomes 𝑓: 0.014 ( 268 hom. )

Consequence

GABRA6
ENST00000274545.10 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.82

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015738577).

BP6

Variant 5-161689666-C-T is Benign according to our data. Variant chr5-161689666-C-T is described in ClinVar as [Benign]. Clinvar id is 477866.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0104 (1581/152146) while in subpopulation SAS AF= 0.0472 (228/4828). AF 95% confidence interval is 0.0422. There are 10 homozygotes in gnomad4. There are 838 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA6	NM_000811.3 linkuse as main transcript	c.560C>T	p.Thr187Met	missense_variant	6/9	ENST00000274545.10	NP_000802.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA6	ENST00000274545.10 linkuse as main transcript	c.560C>T	p.Thr187Met	missense_variant	6/9	1	NM_000811.3	ENSP00000274545	P1

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1582

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00292

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00773

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.00810

Gnomad SAS

AF:

0.0470

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.0154

AC:

3853

AN:

250646

Hom.:

AF XY:

0.0175

AC XY:

2378

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.00244

Gnomad AMR exome

AF:

0.00719

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.00958

Gnomad SAS exome

AF:

0.0488

Gnomad FIN exome

AF:

0.0145

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.0140

AC:

20324

AN:

1456374

Hom.:

268

Cov.:

AF XY:

0.0150

AC XY:

10849

AN XY:

724746

show subpopulations

Gnomad4 AFR exome

AF:

0.00222

Gnomad4 AMR exome

AF:

0.00826

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.00651

Gnomad4 SAS exome

AF:

0.0471

Gnomad4 FIN exome

AF:

0.0122

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.0142

GnomAD4 genome

AF:

0.0104

AC:

1581

AN:

152146

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

838

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00291

Gnomad4 AMR

AF:

0.00772

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.00792

Gnomad4 SAS

AF:

0.0472

Gnomad4 FIN

AF:

0.0184

Gnomad4 NFE

AF:

0.0120

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0131

Hom.:

Bravo

AF:

0.00869

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.00432

AC:

ESP6500EA

AF:

0.0119

AC:

102

ExAC

AF:

0.0154

AC:

1874

Asia WGS

AF:

0.0320

AC:

110

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

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

Aug 16, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;.;.

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

T;D;D;D

MetaRNN

Benign

0.016

T;T;T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

1.8

L;.;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.1

N;N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.064

T;T;T;T

Sift4G

Benign

0.10

T;T;T;T

Polyphen

1.0

D;.;.;.

Vest4

0.33

MPC

0.42

ClinPred

0.017

GERP RS

5.4

Varity_R

0.32

gMVP

0.48

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