4-46402396-A-G

Position:

• chr4-46402396-A-G

Variant summary

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

The ENST00000510861.5(GABRA2):​c.-10-13680T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,948 control chromosomes in the GnomAD database, including 9,396 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 0.34 (9396 hom., cov: 32)
• Consequence: GABRA2 ENST00000510861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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]

(HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.46402396A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000510861.5	c.-10-13680T>C		intron_variant		5		ENSP00000421828.1
ENSG00000249330	ENST00000502455.2	n.438+11388A>G		intron_variant		4
ENSG00000249330	ENST00000651612.1	n.386+11388A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51341 AN: 151830 Hom.: 9371 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.338 AC: 51413 AN: 151948 Hom.: 9396 Cov.: 32 AF XY: 0.348 AC XY: 25845 AN XY: 74258

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.321

Alfa AF: 0.327 Hom.: 2325

Bravo AF: 0.341

Asia WGS AF: 0.623 AC: 2165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.62

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: rs1545234; hg19: chr4-46404413;