5-161685998-G-A

Variant names:

• chr5-161685998-G-A
• rs13188991
• NM_000811.3:c.9G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000811.3(GABRA6):​c.9G>A​(p.Ser3Ser) 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 NM_000811.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.855
• Publications: 16 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 -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 VariationId 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.

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.9G>A	p.Ser3Ser	synonymous	Exon 1 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.9G>A	p.Ser3Ser	synonymous	Exon 1 of 9	ENSP00000274545.5	Q16445
	GABRA6	ENST00000523217.5	TSL:5	c.9G>A	p.Ser3Ser	synonymous	Exon 1 of 9	ENSP00000430527.1	E7EV53
	GABRA6	ENST00000522269.5	TSL:4	n.352-232G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26950 AN: 152006 Hom.: 3113 Cov.: 32

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

GnomAD2 exomes AF: 0.190 AC: 47863 AN: 251412 AF XY: 0.192

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 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.: 31 AF XY: 0.232 AC XY: 168206 AN XY: 726248

African (AFR) AF: 0.0414 AC: 1385 AN: 33462

American (AMR) AF: 0.114 AC: 5095 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 7686 AN: 26116

East Asian (EAS) AF: 0.0672 AC: 2669 AN: 39700

South Asian (SAS) AF: 0.0901 AC: 7768 AN: 86240

European-Finnish (FIN) AF: 0.264 AC: 14094 AN: 53418

Middle Eastern (MID) AF: 0.209 AC: 1207 AN: 5764

European-Non Finnish (NFE) AF: 0.261 AC: 289614 AN: 1110000

Other (OTH) AF: 0.224 AC: 13534 AN: 60342

GnomAD4 genome AF: 0.177 AC: 26949 AN: 152124 Hom.: 3113 Cov.: 32 AF XY: 0.175 AC XY: 12980 AN XY: 74352

African (AFR) AF: 0.0461 AC: 1914 AN: 41538

American (AMR) AF: 0.160 AC: 2440 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 987 AN: 3470

East Asian (EAS) AF: 0.0740 AC: 383 AN: 5174

South Asian (SAS) AF: 0.0850 AC: 410 AN: 4826

European-Finnish (FIN) AF: 0.268 AC: 2832 AN: 10574

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17383 AN: 67958

Other (OTH) AF: 0.173 AC: 364 AN: 2110

Alfa AF: 0.213 Hom.: 8090

Bravo AF: 0.163

Asia WGS AF: 0.0690 AC: 241 AN: 3478

EpiCase AF: 0.248

EpiControl AF: 0.247

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Childhood absence epilepsy (1)
-	-	1	GABRA6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.77
PhyloP100		-0.85
PromoterAI		0.23	Neutral
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13188991; hg19: chr5-161113004; COSMIC: COSV50878128; COSMIC: COSV50878128;