rs253017

Positions:

• chr5-161315949-G-A
• chr5-161315949-G-C
• chr5-161315949-G-T

Variant summary

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

The NM_001371727.1(GABRB2):​c.1191+10419C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,040 control chromosomes in the GnomAD database, including 16,051 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 0.43 (16051 hom., cov: 33)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.1191+10419C>T		intron_variant		ENST00000393959.6	NP_001358656.1
GABRB2	NM_000813.3	c.1077+14934C>T		intron_variant			NP_000804.1
GABRB2	NM_021911.3	c.1191+10419C>T		intron_variant			NP_068711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB2	ENST00000393959.6	c.1191+10419C>T		intron_variant		1	NM_001371727.1	ENSP00000377531

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64807 AN: 151922 Hom.: 16017 Cov.: 33

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.427 AC: 64889 AN: 152040 Hom.: 16051 Cov.: 33 AF XY: 0.426 AC XY: 31631 AN XY: 74316

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.413

Alfa AF: 0.377 Hom.: 1566

Bravo AF: 0.457

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.60

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: rs253017; hg19: chr5-160742956;