4-46254540-A-T

Position:

• chr4-46254540-A-T

Variant summary

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

The ENST00000381620.9(GABRA2):​c.1060-3936T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,090 control chromosomes in the GnomAD database, including 30,070 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 0.62 (30070 hom., cov: 30)
• Consequence: GABRA2 ENST00000381620.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358

Genes affected

GABRA2 (HGNC:4076): (gamma-aminobutyric acid type A receptor subunit alpha2) 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.1060-3936T>A		intron_variant		ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9	c.1060-3936T>A		intron_variant		1	NM_000807.4	ENSP00000371033	P2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94092 AN: 150972 Hom.: 30029 Cov.: 30

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.623 AC: 94176 AN: 151090 Hom.: 30070 Cov.: 30 AF XY: 0.623 AC XY: 45933 AN XY: 73774

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.630

Alfa AF: 0.428 Hom.: 1054

Bravo AF: 0.621

Asia WGS AF: 0.652 AC: 2269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.49

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: rs693547; hg19: chr4-46256557;