rs548583

chr4-46261327-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000515082.5(GABRA2):c.*554T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,916 control chromosomes in the GnomAD database, including 27,860 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 0.60 (27740 hom., cov: 33)
  • Exomes 𝑓: 0.51 (120 hom.)
• Consequence: GABRA2 ENST00000515082.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4	c.1059+599T>C		intron_variant		ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9	c.1059+599T>C		intron_variant		1	NM_000807.4	P2

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91160 AN: 151848 Hom.: 27725 Cov.: 33

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.611

GnomAD4 exome AF: 0.508 AC: 483 AN: 950 Hom.: 120 Cov.: 0 AF XY: 0.525 AC XY: 274 AN XY: 522

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.724

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.538

GnomAD4 genome AF: 0.600 AC: 91214 AN: 151966 Hom.: 27740 Cov.: 33 AF XY: 0.601 AC XY: 44604 AN XY: 74268

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.612

Alfa AF: 0.582 Hom.: 4088

Bravo AF: 0.593

Asia WGS AF: 0.642 AC: 2232 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.1
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs548583; hg19: chr4-46263344;