rs279867

Variant names:

• chr4-46306286-A-C
• rs279867
• NM_000807.4:c.560-575T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-46306286-A-C
• chr4-46306286-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.560-575T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,030 control chromosomes in the GnomAD database, including 12,225 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 0.39 (12225 hom., cov: 32)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.792
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.560-575T>G		intron_variant	Intron 6 of 9	ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9	c.560-575T>G		intron_variant	Intron 6 of 9	1	NM_000807.4	ENSP00000371033.4

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59777 AN: 151912 Hom.: 12205 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.394 AC: 59833 AN: 152030 Hom.: 12225 Cov.: 32 AF XY: 0.394 AC XY: 29229 AN XY: 74278

African (AFR) AF: 0.306 AC: 12706 AN: 41492

American (AMR) AF: 0.453 AC: 6909 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1058 AN: 3468

East Asian (EAS) AF: 0.522 AC: 2697 AN: 5162

South Asian (SAS) AF: 0.242 AC: 1166 AN: 4824

European-Finnish (FIN) AF: 0.415 AC: 4379 AN: 10558

Middle Eastern (MID) AF: 0.366 AC: 106 AN: 290

European-Non Finnish (NFE) AF: 0.436 AC: 29661 AN: 67952

Other (OTH) AF: 0.381 AC: 805 AN: 2112

Alfa AF: 0.418 Hom.: 2393

Bravo AF: 0.400

Asia WGS AF: 0.376 AC: 1307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.0
DANN	Benign	0.29
PhyloP100		0.79
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: rs279867; hg19: chr4-46308303;