rs279866

Positions:

• chr4-46307747-A-G

Variant summary

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

The NM_000807.4(GABRA2):​c.560-2036T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,040 control chromosomes in the GnomAD database, including 12,229 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 0.39 (12229 hom., cov: 32)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.560-2036T>C		intron_variant		ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9	c.560-2036T>C		intron_variant		1	NM_000807.4	ENSP00000371033	P2

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59782 AN: 151922 Hom.: 12209 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.394 AC: 59838 AN: 152040 Hom.: 12229 Cov.: 32 AF XY: 0.394 AC XY: 29250 AN XY: 74312

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.382

Alfa AF: 0.416 Hom.: 1695

Bravo AF: 0.400

Asia WGS AF: 0.375 AC: 1301 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.67

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: rs279866; hg19: chr4-46309764;