rs548260

Positions:

• chr4-46266467-G-A
• chr4-46266467-G-C
• chr4-46266467-G-T

Variant summary

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

The NM_000807.4(GABRA2):​c.857-4339C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 149,690 control chromosomes in the GnomAD database, including 30,093 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 0.63 (30093 hom., cov: 29)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4	c.857-4339C>T		intron_variant		ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9	c.857-4339C>T		intron_variant		1	NM_000807.4	P2

Frequencies

GnomAD3 genomes AF: 0.627 AC: 93797 AN: 149622 Hom.: 30066 Cov.: 29

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.641

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.627 AC: 93845 AN: 149690 Hom.: 30093 Cov.: 29 AF XY: 0.627 AC XY: 45759 AN XY: 73012

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.633

Alfa AF: 0.584 Hom.: 5189

Bravo AF: 0.623

Asia WGS AF: 0.654 AC: 2270 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.86
DANN	Benign	0.13

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: rs548260; hg19: chr4-46268484;