rs16859227

Positions:

• chr4-46248588-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000807.4(GABRA2):​c.*1720G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,176 control chromosomes in the GnomAD database, including 3,315 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 0.20 (3315 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: GABRA2 NM_000807.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.*1720G>A		3_prime_UTR_variant	10/10	ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620	c.*1720G>A		3_prime_UTR_variant	10/10	1	NM_000807.4	ENSP00000371033.4
GABRA2	ENST00000510861	c.*1720G>A		3_prime_UTR_variant	10/10	5		ENSP00000421828.1
GABRA2	ENST00000514090	c.*1720G>A		3_prime_UTR_variant	10/10	5		ENSP00000421300.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30072 AN: 151058 Hom.: 3313 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.199 AC: 30094 AN: 151176 Hom.: 3315 Cov.: 33 AF XY: 0.195 AC XY: 14393 AN XY: 73816

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.0592

Gnomad4 SAS AF: 0.0991

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.218

Alfa AF: 0.238 Hom.: 5708

Bravo AF: 0.206

Asia WGS AF: 0.0880 AC: 306 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	12
DANN	Benign	0.62

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: rs16859227; hg19: chr4-46250605;