chr4-46285058-T-G

Variant names:

• chr4-46285058-T-G
• rs483160
• NM_000807.4:c.856+18402A>C

Variant summary

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

The NM_000807.4(GABRA2):​c.856+18402A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 148,290 control chromosomes in the GnomAD database, including 28,046 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 0.61 (28046 hom., cov: 26)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.856+18402A>C		intron_variant	Intron 8 of 9	ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9	c.856+18402A>C		intron_variant	Intron 8 of 9	1	NM_000807.4	ENSP00000371033.4

Frequencies

GnomAD3 genomes AF: 0.609 AC: 90330 AN: 148224 Hom.: 28041 Cov.: 26

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.645

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.609 AC: 90347 AN: 148290 Hom.: 28046 Cov.: 26 AF XY: 0.609 AC XY: 43943 AN XY: 72158

African (AFR) AF: 0.704 AC: 28515 AN: 40476

American (AMR) AF: 0.547 AC: 8181 AN: 14960

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2402 AN: 3454

East Asian (EAS) AF: 0.496 AC: 2502 AN: 5048

South Asian (SAS) AF: 0.757 AC: 3603 AN: 4758

European-Finnish (FIN) AF: 0.578 AC: 5224 AN: 9044

Middle Eastern (MID) AF: 0.628 AC: 181 AN: 288

European-Non Finnish (NFE) AF: 0.563 AC: 37888 AN: 67284

Other (OTH) AF: 0.623 AC: 1293 AN: 2074

Alfa AF: 0.458 Hom.: 1303

Bravo AF: 0.605

Asia WGS AF: 0.630 AC: 2185 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		-0.084
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: rs483160; hg19: chr4-46287075;