rs76773579

Variant names:

• chr5-161690237-A-G
• rs76773579
• NM_000811.3:c.710A>G
• GABRA6 p.Gln237Arg

Your query was ambiguous. Multiple possible variants found:

• chr5-161690237-A-G
• chr5-161690237-A-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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. 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 7.41
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 477869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000811.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA6	NM_000811.3	MANE Select	c.710A>G	p.Gln237Arg	missense	Exon 7 of 9	NP_000802.2	Q16445

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA6	ENST00000274545.10	TSL:1 MANE Select	c.710A>G	p.Gln237Arg	missense	Exon 7 of 9	ENSP00000274545.5	Q16445
	GABRA6	ENST00000523217.5	TSL:5	c.680A>G	p.Gln227Arg	missense	Exon 7 of 9	ENSP00000430527.1	E7EV53
	GABRA6	ENST00000520000.5	TSL:4	c.527A>G	p.Gln176Arg	missense	Exon 5 of 5	ENSP00000429943.1	H0YBP3

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 345 AN: 152192 Hom.: 5 Cov.: 32

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

GnomAD2 exomes AF: 0.00309 AC: 776 AN: 251374 AF XY: 0.00324

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 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.: 10 Cov.: 31 AF XY: 0.00306 AC XY: 2226 AN XY: 727046

African (AFR) AF: 0.000448 AC: 15 AN: 33472

American (AMR) AF: 0.00130 AC: 58 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00207 AC: 54 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.00356 AC: 307 AN: 86248

European-Finnish (FIN) AF: 0.00530 AC: 283 AN: 53388

Middle Eastern (MID) AF: 0.00399 AC: 23 AN: 5762

European-Non Finnish (NFE) AF: 0.00303 AC: 3365 AN: 1111740

Other (OTH) AF: 0.00234 AC: 141 AN: 60382

GnomAD4 genome AF: 0.00227 AC: 345 AN: 152310 Hom.: 5 Cov.: 32 AF XY: 0.00215 AC XY: 160 AN XY: 74474

African (AFR) AF: 0.000529 AC: 22 AN: 41576

American (AMR) AF: 0.00105 AC: 16 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4832

European-Finnish (FIN) AF: 0.00386 AC: 41 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00366 AC: 249 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00302 Hom.: 3

Bravo AF: 0.00197

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00311

EpiControl AF: 0.00326

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Childhood absence epilepsy (1)
-	-	1	GABRA6-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	T
Eigen	Benign	-0.072
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.16	N
PhyloP100		7.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.090	N
REVEL	Uncertain	0.34
Sift	Benign	0.17	T
Sift4G	Benign	0.23	T
Varity_R		0.26
gMVP		0.74
Mutation Taster		=74/26	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs76773579;

hg19: chr5-161117243;

COSMIC: COSV105098644;

COSMIC: COSV105098644;