rs11503015

Variant names:

• chr4-46386027-A-G
• rs11503015
• NM_000807.4:c.187+47T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-46386027-A-G
• chr4-46386027-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.187+47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 1,124,930 control chromosomes in the GnomAD database, including 2,167 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 0.049 (220 hom., cov: 32)
  • Exomes 𝑓: 0.060 (1947 hom.)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• 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=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.187+47T>C		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.187+47T>C		intron_variant	Intron 3 of 9	1	NM_000807.4	ENSP00000371033.4

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7448 AN: 152066 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0402

Gnomad ASJ AF: 0.0681

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.0933

Gnomad FIN AF: 0.0487

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0638

Gnomad OTH AF: 0.0503

GnomAD2 exomes AF: 0.0561 AC: 12835 AN: 228854 AF XY: 0.0593

Gnomad AFR exome AF: 0.0208

Gnomad AMR exome AF: 0.0334

Gnomad ASJ exome AF: 0.0734

Gnomad EAS exome AF: 0.0210

Gnomad FIN exome AF: 0.0462

Gnomad NFE exome AF: 0.0639

Gnomad OTH exome AF: 0.0604

GnomAD4 exome AF: 0.0596 AC: 57951 AN: 972746 Hom.: 1947 Cov.: 13 AF XY: 0.0615 AC XY: 31021 AN XY: 504680

African (AFR) AF: 0.0212 AC: 485 AN: 22828

American (AMR) AF: 0.0334 AC: 1348 AN: 40300

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 1636 AN: 22716

East Asian (EAS) AF: 0.0119 AC: 435 AN: 36650

South Asian (SAS) AF: 0.0896 AC: 6584 AN: 73498

European-Finnish (FIN) AF: 0.0488 AC: 2569 AN: 52652

Middle Eastern (MID) AF: 0.0803 AC: 389 AN: 4844

European-Non Finnish (NFE) AF: 0.0622 AC: 42023 AN: 675198

Other (OTH) AF: 0.0563 AC: 2482 AN: 44060

GnomAD4 genome AF: 0.0489 AC: 7446 AN: 152184 Hom.: 220 Cov.: 32 AF XY: 0.0485 AC XY: 3609 AN XY: 74394

African (AFR) AF: 0.0219 AC: 909 AN: 41546

American (AMR) AF: 0.0402 AC: 615 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0681 AC: 236 AN: 3468

East Asian (EAS) AF: 0.0183 AC: 95 AN: 5180

South Asian (SAS) AF: 0.0934 AC: 450 AN: 4818

European-Finnish (FIN) AF: 0.0487 AC: 516 AN: 10596

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0638 AC: 4336 AN: 67982

Other (OTH) AF: 0.0498 AC: 105 AN: 2108

Alfa AF: 0.0378 Hom.: 31

Bravo AF: 0.0452

Asia WGS AF: 0.0490 AC: 170 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		0.27
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: rs11503015; hg19: chr4-46388044;