chr4-46354935-C-T

Position:

• chr4-46354935-C-T

Variant summary

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

The NM_000807.4(GABRA2):​c.188-22253G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,950 control chromosomes in the GnomAD database, including 25,362 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 0.58 (25362 hom., cov: 32)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRA2	NM_000807.4	c.188-22253G>A		intron_variant		ENST00000381620.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRA2	ENST00000381620.9	c.188-22253G>A		intron_variant		1	NM_000807.4	P2

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87315 AN: 151832 Hom.: 25338 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.575 AC: 87380 AN: 151950 Hom.: 25362 Cov.: 32 AF XY: 0.575 AC XY: 42668 AN XY: 74232

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.593

Alfa AF: 0.391 Hom.: 680

Bravo AF: 0.608

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1442059; hg19: chr4-46356952;