chr4-46279102-C-T

Variant names:

• chr4-46279102-C-T
• rs530329
• NM_000807.4:c.857-16974G>A

Variant summary

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

The NM_000807.4(GABRA2):​c.857-16974G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 151,824 control chromosomes in the GnomAD database, including 29,053 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 0.61 (29053 hom., cov: 32)
• Consequence: GABRA2 NM_000807.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRA2	NM_000807.4	c.857-16974G>A		intron_variant	Intron 8 of 9	ENST00000381620.9	NP_000798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRA2	ENST00000381620.9	c.857-16974G>A		intron_variant	Intron 8 of 9	1	NM_000807.4	ENSP00000371033.4

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93052 AN: 151706 Hom.: 29027 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.613 AC: 93117 AN: 151824 Hom.: 29053 Cov.: 32 AF XY: 0.613 AC XY: 45448 AN XY: 74146

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.622

Alfa AF: 0.587 Hom.: 4583

Bravo AF: 0.607

Asia WGS AF: 0.632 AC: 2198 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
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: rs530329; hg19: chr4-46281119;