chr4-46402396-A-G

Variant names:

• chr4-46402396-A-G
• rs1545234
• ENST00000510861.5:c.-10-13680T>C

Variant summary

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

The ENST00000510861.5(GABRA2):​c.-10-13680T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,948 control chromosomes in the GnomAD database, including 9,396 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 0.34 (9396 hom., cov: 32)
• Consequence: GABRA2 ENST00000510861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• 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

ENSG00000249330 (HGNC:40247):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000510861.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRA2	ENST00000510861.5	TSL:5	c.-10-13680T>C		intron	N/A	ENSP00000421828.1
	ENSG00000249330	ENST00000502455.2	TSL:4	n.438+11388A>G		intron	N/A
	ENSG00000249330	ENST00000651612.1		n.386+11388A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51341 AN: 151830 Hom.: 9371 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.338 AC: 51413 AN: 151948 Hom.: 9396 Cov.: 32 AF XY: 0.348 AC XY: 25845 AN XY: 74258

African (AFR) AF: 0.289 AC: 11958 AN: 41440

American (AMR) AF: 0.449 AC: 6858 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 744 AN: 3470

East Asian (EAS) AF: 0.696 AC: 3568 AN: 5128

South Asian (SAS) AF: 0.526 AC: 2533 AN: 4818

European-Finnish (FIN) AF: 0.360 AC: 3797 AN: 10550

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21025 AN: 67960

Other (OTH) AF: 0.321 AC: 676 AN: 2108

Alfa AF: 0.327 Hom.: 2367

Bravo AF: 0.341

Asia WGS AF: 0.623 AC: 2165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.62
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: rs1545234; hg19: chr4-46404413;