rs2165607

Variant names:

• chr4-46398204-T-C
• rs2165607
• ENST00000510861.5:c.-10-9488A>G

Variant summary

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

The ENST00000510861.5(GABRA2):​c.-10-9488A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0627 in 152,250 control chromosomes in the GnomAD database, including 400 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 0.063 (400 hom., cov: 32)
• Consequence: GABRA2 ENST00000510861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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]

ENSG00000249330 (HGNC:):

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 = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000510861.5	c.-10-9488A>G		intron_variant	Intron 1 of 9	5		ENSP00000421828.1
ENSG00000249330	ENST00000502455.2	n.438+7196T>C		intron_variant	Intron 2 of 2	4
ENSG00000249330	ENST00000651612.1	n.386+7196T>C		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9562 AN: 152132 Hom.: 401 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.0948

Gnomad EAS AF: 0.0467

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0708

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

GnomAD4 genome AF: 0.0627 AC: 9545 AN: 152250 Hom.: 400 Cov.: 32 AF XY: 0.0649 AC XY: 4829 AN XY: 74438

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.0869

Gnomad4 ASJ AF: 0.0948

Gnomad4 EAS AF: 0.0468

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.0587

Gnomad4 NFE AF: 0.0732

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0613 Hom.: 64

Bravo AF: 0.0613

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.097
DANN	Benign	0.71

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: rs2165607; hg19: chr4-46400221;