rs279828

Variant names:

• chr4-46332793-A-C
• rs279828
• NM_000807.4:c.188-111T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-46332793-A-C
• chr4-46332793-A-G

Variant summary

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

The NM_000807.4(GABRA2):​c.188-111T>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
• Publications: 12 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=-0.9).
• 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 rank	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.188-111T>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.188-111T>G		intron_variant	Intron 3 of 9	1	NM_000807.4	ENSP00000371033.4

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

African (AFR) AF: 0.297 AC: 3245 AN: 10914

American (AMR) AF: 0.495 AC: 9185 AN: 18558

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 4364 AN: 13580

East Asian (EAS) AF: 0.514 AC: 14587 AN: 28396

South Asian (SAS) AF: 0.294 AC: 10252 AN: 34906

European-Finnish (FIN) AF: 0.473 AC: 20149 AN: 42592

Middle Eastern (MID) AF: 0.281 AC: 520 AN: 1850

European-Non Finnish (NFE) AF: 0.438 AC: 115910 AN: 264628

Other (OTH) AF: 0.428 AC: 10193 AN: 23814

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

African (AFR) AF: 0.307 AC: 12711 AN: 41450

American (AMR) AF: 0.470 AC: 7159 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3468

East Asian (EAS) AF: 0.571 AC: 2946 AN: 5158

South Asian (SAS) AF: 0.320 AC: 1537 AN: 4810

European-Finnish (FIN) AF: 0.471 AC: 4982 AN: 10570

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31009 AN: 67918

Other (OTH) AF: 0.397 AC: 840 AN: 2114

Alfa AF: 0.434 Hom.: 2326

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
PhyloP100		-0.10
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: rs279828; hg19: chr4-46334810;