rs2165607

chr4-46398204-T-C

Variant summary

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

The ENST00000651612.1(ENSG00000249330):n.386+7196T>C 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 0.0627 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: ENST00000651612.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.92).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000651612.1	n.386+7196T>C		intron_variant, non_coding_transcript_variant
GABRA2	ENST00000510861.5	c.-10-9488A>G		intron_variant		5		P2
	ENST00000502455.2	n.438+7196T>C		intron_variant, non_coding_transcript_variant		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;