chr4-46398314-A-G

Position:

• chr4-46398314-A-G

Variant summary

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

The ENST00000651612.1(ENSG00000249330):​n.386+7306A>G 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 0.628 in 152,042 control chromosomes in the GnomAD database, including 30,032 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 0.63 (30032 hom., cov: 32)
• Consequence: ENST00000651612.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000651612.1	n.386+7306A>G		intron_variant, non_coding_transcript_variant
GABRA2	ENST00000510861.5	c.-10-9598T>C		intron_variant		5		ENSP00000421828	P2
	ENST00000502455.2	n.438+7306A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95330 AN: 151924 Hom.: 29993 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.628 AC: 95426 AN: 152042 Hom.: 30032 Cov.: 32 AF XY: 0.628 AC XY: 46679 AN XY: 74314

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.623

Alfa AF: 0.631 Hom.: 40512

Bravo AF: 0.633

Asia WGS AF: 0.706 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.50
DANN	Benign	0.45

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: rs1025852; hg19: chr4-46400331;