rs279871

Variant names:

• chr4-46303716-T-C
• rs279871
• NM_000807.4:c.704-104A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-46303716-T-C
• chr4-46303716-T-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.704-104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 951,780 control chromosomes in the GnomAD database, including 87,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.38 (11724 hom., cov: 32)
  • Exomes 𝑓: 0.43 (75560 hom.)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -1.83
• Publications: 62 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.704-104A>G		intron_variant	Intron 7 of 9	ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9	c.704-104A>G		intron_variant	Intron 7 of 9	1	NM_000807.4	ENSP00000371033.4

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57974 AN: 151964 Hom.: 11711 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.431 AC: 344593 AN: 799698 Hom.: 75560 AF XY: 0.424 AC XY: 172842 AN XY: 408082

African (AFR) AF: 0.269 AC: 4898 AN: 18224

American (AMR) AF: 0.482 AC: 10574 AN: 21924

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 5326 AN: 16772

East Asian (EAS) AF: 0.490 AC: 16378 AN: 33458

South Asian (SAS) AF: 0.249 AC: 13620 AN: 54668

European-Finnish (FIN) AF: 0.423 AC: 18676 AN: 44166

Middle Eastern (MID) AF: 0.290 AC: 934 AN: 3224

European-Non Finnish (NFE) AF: 0.454 AC: 258481 AN: 569786

Other (OTH) AF: 0.419 AC: 15706 AN: 37476

GnomAD4 genome AF: 0.381 AC: 58008 AN: 152082 Hom.: 11724 Cov.: 32 AF XY: 0.382 AC XY: 28381 AN XY: 74342

African (AFR) AF: 0.263 AC: 10901 AN: 41502

American (AMR) AF: 0.451 AC: 6890 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3468

East Asian (EAS) AF: 0.522 AC: 2698 AN: 5170

South Asian (SAS) AF: 0.241 AC: 1164 AN: 4822

European-Finnish (FIN) AF: 0.416 AC: 4394 AN: 10570

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29658 AN: 67952

Other (OTH) AF: 0.376 AC: 794 AN: 2112

Alfa AF: 0.423 Hom.: 15719

Bravo AF: 0.386

Asia WGS AF: 0.371 AC: 1287 AN: 3476

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Alcoholism, susceptibility to Other:1

Apr 01, 2004

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.071
DANN	Benign	0.38
PhyloP100		-1.8
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: rs279871; hg19: chr4-46305733;