rs279828

chr4-46332793-A-C

Variant summary

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

The NM_000807.4(GABRA2):c.188-111T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 591,170 control chromosomes in the GnomAD database, including 54,964 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 0.41 (13459 hom., cov: 31)
  • Exomes 𝑓: 0.43 (41505 hom.)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4	c.188-111T>G		intron_variant		ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9	c.188-111T>G		intron_variant		1	NM_000807.4	P2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62717 AN: 151814 Hom.: 13440 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.429 AC: 188405 AN: 439238 Hom.: 41505 AF XY: 0.422 AC XY: 98957 AN XY: 234344

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.495

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.473

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.413 AC: 62758 AN: 151932 Hom.: 13459 Cov.: 31 AF XY: 0.416 AC XY: 30874 AN XY: 74272

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.397

Alfa AF: 0.438 Hom.: 2286

Bravo AF: 0.413

Asia WGS AF: 0.431 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.7
Dann	Benign	0.35

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: rs279828; hg19: chr4-46334810;