rs426463

Variant names:

• chr4-46343943-A-C
• rs426463
• NM_000807.4:c.188-11261T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-46343943-A-C
• chr4-46343943-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000807.4(GABRA2):​c.188-11261T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,198 control chromosomes in the GnomAD database, including 16,331 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 0.46 (16331 hom., cov: 31)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 4 publications found

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]

GABRA2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 78

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.188-11261T>G		intron_variant	Intron 3 of 9	ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9	c.188-11261T>G		intron_variant	Intron 3 of 9	1	NM_000807.4	ENSP00000371033.4

Frequencies

GnomAD3 genomes AF: 0.463 AC: 69955 AN: 151080 Hom.: 16298 Cov.: 31

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.463 AC: 70034 AN: 151198 Hom.: 16331 Cov.: 31 AF XY: 0.464 AC XY: 34253 AN XY: 73846

African (AFR) AF: 0.486 AC: 20015 AN: 41200

American (AMR) AF: 0.489 AC: 7414 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1112 AN: 3460

East Asian (EAS) AF: 0.557 AC: 2824 AN: 5072

South Asian (SAS) AF: 0.320 AC: 1542 AN: 4812

European-Finnish (FIN) AF: 0.468 AC: 4912 AN: 10506

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30855 AN: 67674

Other (OTH) AF: 0.432 AC: 907 AN: 2100

Alfa AF: 0.434 Hom.: 5517

Bravo AF: 0.472

Asia WGS AF: 0.440 AC: 1528 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.56
DANN	Benign	0.54
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs426463; hg19: chr4-46345960;