ENST00000518888.1:n.293-1531G>A

Variant names:

• chr5-161684168-G-A
• rs1992647
• ENST00000518888.1:n.293-1531G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000518888.1(GABRA6):​n.293-1531G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 150,542 control chromosomes in the GnomAD database, including 24,759 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 0.57 (24759 hom., cov: 31)
• Consequence: GABRA6 ENST00000518888.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA6	ENST00000518888.1	n.293-1531G>A		intron_variant	Intron 3 of 3	4
GABRA6	ENST00000522269.5	n.352-2062G>A		intron_variant	Intron 4 of 6	4

Frequencies

GnomAD3 genomes AF: 0.570 AC: 85676 AN: 150418 Hom.: 24757 Cov.: 31

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.569 AC: 85697 AN: 150542 Hom.: 24759 Cov.: 31 AF XY: 0.566 AC XY: 41535 AN XY: 73404

African (AFR) AF: 0.485 AC: 19971 AN: 41190

American (AMR) AF: 0.521 AC: 7731 AN: 14844

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2193 AN: 3456

East Asian (EAS) AF: 0.362 AC: 1811 AN: 4998

South Asian (SAS) AF: 0.476 AC: 2278 AN: 4788

European-Finnish (FIN) AF: 0.620 AC: 6394 AN: 10316

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.642 AC: 43492 AN: 67698

Other (OTH) AF: 0.568 AC: 1176 AN: 2072

Alfa AF: 0.602 Hom.: 45465

Bravo AF: 0.550

Asia WGS AF: 0.397 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.84
DANN	Benign	0.69
PhyloP100		0.0040

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1992647; hg19: chr5-161111174; COSMIC: COSV50878699;