rs1992647

chr5-161684168-G-A

Variant summary

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

The ENST00000518888.1(GABRA6):n.293-1531G>A variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

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=-0.98).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA6	ENST00000518888.1	n.293-1531G>A		intron_variant, non_coding_transcript_variant		4
GABRA6	ENST00000522269.5	n.352-2062G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.568

Alfa AF: 0.598 Hom.: 3573

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

Splicing

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

Publications

LitVar

Other links and lift over

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