rs11503014

Positions:

• chr4-46388848-C-G

Variant summary

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

The NM_000807.4(GABRA2):​c.-10-132G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,437,656 control chromosomes in the GnomAD database, including 57,351 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 0.27 (5579 hom., cov: 32)
  • Exomes 𝑓: 0.28 (51772 hom.)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4	c.-10-132G>C		intron_variant		ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9	c.-10-132G>C		intron_variant		1	NM_000807.4	P2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40824 AN: 151984 Hom.: 5569 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0892

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.284 AC: 364587 AN: 1285554 Hom.: 51772 Cov.: 30 AF XY: 0.282 AC XY: 176160 AN XY: 625176

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.269 AC: 40865 AN: 152102 Hom.: 5579 Cov.: 32 AF XY: 0.260 AC XY: 19298 AN XY: 74346

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.0883

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.283

Alfa AF: 0.270 Hom.: 677

Bravo AF: 0.270

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.1
DANN	Benign	0.58

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: rs11503014; hg19: chr4-46390865;