4-46391595-T-C

Position:

• chr4-46391595-T-C

Variant summary

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

The ENST00000510861.5(GABRA2):​c.-10-2879A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,184 control chromosomes in the GnomAD database, including 53,738 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 0.84 (53738 hom., cov: 33)
• Consequence: GABRA2 ENST00000510861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.46391595T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000510861.5	c.-10-2879A>G		intron_variant		5		ENSP00000421828.1
ENSG00000249330	ENST00000502455.2	n.438+587T>C		intron_variant		4
ENSG00000249330	ENST00000651612.1	n.386+587T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127429 AN: 152066 Hom.: 53675 Cov.: 33

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.838 AC: 127554 AN: 152184 Hom.: 53738 Cov.: 33 AF XY: 0.841 AC XY: 62544 AN XY: 74390

Gnomad4 AFR AF: 0.931

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.826

Alfa AF: 0.797 Hom.: 45502

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.3
DANN	Benign	0.65

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;