rs6896733

Positions:

• chr5-161427212-C-T

Variant summary

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

The NM_001371727.1(GABRB2):​c.459-16155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,970 control chromosomes in the GnomAD database, including 16,177 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 0.44 (16177 hom., cov: 32)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

Genes affected

GABRB2 (HGNC:4082): (gamma-aminobutyric acid type A receptor subunit beta2) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 2 subunit. It is mapped to chromosome 5q34 in a cluster comprised of genes encoding alpha 1 and gamma 2 subunits of the GABA A receptor. Alternative splicing of this gene generates 2 transcript variants, differing by a 114 bp insertion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.459-16155G>A		intron_variant		ENST00000393959.6	NP_001358656.1
GABRB2	NM_000813.3	c.459-16155G>A		intron_variant			NP_000804.1
GABRB2	NM_021911.3	c.459-16155G>A		intron_variant			NP_068711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB2	ENST00000393959.6	c.459-16155G>A		intron_variant		1	NM_001371727.1	ENSP00000377531

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66224 AN: 151852 Hom.: 16146 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.436 AC: 66304 AN: 151970 Hom.: 16177 Cov.: 32 AF XY: 0.433 AC XY: 32166 AN XY: 74256

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.441

Alfa AF: 0.370 Hom.: 3465

Bravo AF: 0.456

Asia WGS AF: 0.355 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.37

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: rs6896733; hg19: chr5-160854218;