rs2119767

Positions:

• chr4-46389556-T-A
• chr4-46389556-T-G

Variant summary

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

The NM_000807.4(GABRA2):​c.-11+179A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 408,946 control chromosomes in the GnomAD database, including 17,565 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 (6710 hom., cov: 29)
  • Exomes 𝑓: 0.28 (10855 hom.)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.-11+179A>T		intron_variant		ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9	c.-11+179A>T		intron_variant		1	NM_000807.4	ENSP00000371033	P2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41038 AN: 151448 Hom.: 6695 Cov.: 29

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0980

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.278 AC: 71543 AN: 257380 Hom.: 10855 Cov.: 5 AF XY: 0.277 AC XY: 33779 AN XY: 122120

Gnomad4 AFR exome AF: 0.0892

Gnomad4 AMR exome AF: 0.460

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.636

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.277

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.271 AC: 41065 AN: 151566 Hom.: 6710 Cov.: 29 AF XY: 0.281 AC XY: 20809 AN XY: 73978

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.279

Alfa AF: 0.263 Hom.: 767

Bravo AF: 0.274

Asia WGS AF: 0.546 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.74

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: rs2119767; hg19: chr4-46391573;