5-161695842-G-C

Position:

• chr5-161695842-G-C

Variant summary

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

The NM_000811.3(GABRA6):​c.1086+3642G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,302 control chromosomes in the GnomAD database, including 24,677 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 (24677 hom., cov: 30)
• Consequence: GABRA6 NM_000811.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413

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]

GABRA6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA6	NM_000811.3	c.1086+3642G>C		intron_variant		ENST00000274545.10	NP_000802.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA6	ENST00000274545.10	c.1086+3642G>C		intron_variant		1	NM_000811.3	ENSP00000274545.5
GABRA6	ENST00000523217.5	c.1056+3642G>C		intron_variant		5		ENSP00000430527.1
GABRA6	ENST00000521520.1	n.1079+3642G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85399 AN: 151188 Hom.: 24675 Cov.: 30

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.565 AC: 85419 AN: 151302 Hom.: 24677 Cov.: 30 AF XY: 0.561 AC XY: 41433 AN XY: 73888

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.560

Alfa AF: 0.595 Hom.: 3263

Bravo AF: 0.549

Asia WGS AF: 0.376 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.32

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: rs6883829; hg19: chr5-161122848; COSMIC: COSV50878784;