rs3811991

chr5-161701403-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000811.3(GABRA6):c.1087-95A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,345,212 control chromosomes in the GnomAD database, including 248,590 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (24712 hom., cov: 33)
  • Exomes 𝑓: 0.61 (223878 hom.)
• Consequence: GABRA6 NM_000811.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA6	NM_000811.3	c.1087-95A>C		intron_variant		ENST00000274545.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA6	ENST00000274545.10	c.1087-95A>C		intron_variant		1	NM_000811.3	P1
GABRA6	ENST00000523217.5	c.1057-95A>C		intron_variant		5
GABRA6	ENST00000521520.1	n.1080-95A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85547 AN: 151970 Hom.: 24710 Cov.: 33

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.566

GnomAD4 exome AF: 0.606 AC: 722780 AN: 1193124 Hom.: 223878 AF XY: 0.604 AC XY: 366914 AN XY: 607300

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.628

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.643

Gnomad4 OTH exome AF: 0.591

GnomAD4 genome AF: 0.563 AC: 85568 AN: 152088 Hom.: 24712 Cov.: 33 AF XY: 0.558 AC XY: 41517 AN XY: 74352

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.560

Alfa AF: 0.583 Hom.: 5015

Bravo AF: 0.549

Asia WGS AF: 0.377 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.6
Dann	Benign	0.54

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

Other links and lift over

dbSNP: rs3811991; hg19: chr5-161128409; COSMIC: COSV50878818;