rs92516

Positions:

• chr5-161313192-C-A
• chr5-161313192-C-T

Variant summary

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

The ENST00000393959.6(GABRB2):​c.1191+13176G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,914 control chromosomes in the GnomAD database, including 21,596 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 0.50 (21596 hom., cov: 31)
• Consequence: GABRB2 ENST00000393959.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.1191+13176G>T		intron_variant		ENST00000393959.6	NP_001358656.1
GABRB2	NM_000813.3	c.1077+17691G>T		intron_variant			NP_000804.1
GABRB2	NM_021911.3	c.1191+13176G>T		intron_variant			NP_068711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB2	ENST00000393959.6	c.1191+13176G>T		intron_variant		1	NM_001371727.1	ENSP00000377531

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76500 AN: 151796 Hom.: 21551 Cov.: 31

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.504 AC: 76597 AN: 151914 Hom.: 21596 Cov.: 31 AF XY: 0.506 AC XY: 37532 AN XY: 74242

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.488

Alfa AF: 0.388 Hom.: 4526

Bravo AF: 0.527

Asia WGS AF: 0.444 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.65
DANN	Benign	0.48

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: rs92516; hg19: chr5-160740199;