rs894269

chr4-46391595-T-Achr4-46391595-T-Cchr4-46391595-T-G

Variant summary

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

The ENST00000651612.1(ENSG00000249330):n.386+587T>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 152,220 control chromosomes in the GnomAD database, including 217 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 0.048 (217 hom., cov: 33)
• Consequence: ENST00000651612.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

Genes affected

(HGNC:):

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000651612.1	n.386+587T>A		intron_variant, non_coding_transcript_variant
GABRA2	ENST00000510861.5	c.-10-2879A>T		intron_variant		5		P2
	ENST00000502455.2	n.438+587T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7357 AN: 152102 Hom.: 218 Cov.: 33

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.0926

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0627

Gnomad OTH AF: 0.0511

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

GnomAD4 genome AF: 0.0483 AC: 7354 AN: 152220 Hom.: 217 Cov.: 33 AF XY: 0.0476 AC XY: 3540 AN XY: 74412

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.0403

Gnomad4 ASJ AF: 0.0651

Gnomad4 EAS AF: 0.0266

Gnomad4 SAS AF: 0.0925

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.0627

Gnomad4 OTH AF: 0.0506

Alfa AF: 0.00238 Hom.: 45502

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	3.1
Dann	Benign	0.61

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: rs894269; hg19: chr4-46393612;