4-46364050-G-A

Variant names:

• chr4-46364050-G-A
• rs1442060
• ENST00000507460.1:c.*4922C>T

Variant summary

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

The ENST00000507460.1(GABRA2):​c.*4922C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,934 control chromosomes in the GnomAD database, including 22,025 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 0.53 (22025 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GABRA2 ENST00000507460.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 12 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 (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.187+22024C>T		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+22024C>T		intron_variant	Intron 3 of 9	1	NM_000807.4	ENSP00000371033.4

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80963 AN: 151816 Hom.: 21983 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.508

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.534 AC: 81063 AN: 151934 Hom.: 22025 Cov.: 32 AF XY: 0.529 AC XY: 39290 AN XY: 74246

African (AFR) AF: 0.627 AC: 25992 AN: 41434

American (AMR) AF: 0.554 AC: 8455 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1424 AN: 3468

East Asian (EAS) AF: 0.624 AC: 3217 AN: 5152

South Asian (SAS) AF: 0.379 AC: 1829 AN: 4822

European-Finnish (FIN) AF: 0.448 AC: 4730 AN: 10554

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33676 AN: 67936

Other (OTH) AF: 0.506 AC: 1066 AN: 2108

Alfa AF: 0.503 Hom.: 30580

Bravo AF: 0.552

Asia WGS AF: 0.492 AC: 1709 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.62
PhyloP100		-0.055
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: rs1442060; hg19: chr4-46366067;