rs252944

Positions:

• chr5-161331330-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001371727.1(GABRB2):​c.833-203G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,036 control chromosomes in the GnomAD database, including 1,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1476 hom., cov: 32)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.43

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]

GABRB2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 5-161331330-C-G is Benign according to our data. Variant chr5-161331330-C-G is described in ClinVar as [Benign]. Clinvar id is 681752.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.833-203G>C		intron_variant		ENST00000393959.6	NP_001358656.1
GABRB2	NM_021911.3	c.833-203G>C		intron_variant			NP_068711.1
GABRB2	NM_000813.3	c.833-203G>C		intron_variant			NP_000804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRB2	ENST00000393959.6	c.833-203G>C		intron_variant		1	NM_001371727.1	ENSP00000377531.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20959 AN: 151918 Hom.: 1473 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.138 AC: 20974 AN: 152036 Hom.: 1476 Cov.: 32 AF XY: 0.139 AC XY: 10307 AN XY: 74306

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.111

Alfa AF: 0.141 Hom.: 196

Bravo AF: 0.140

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.11
DANN	Benign	0.40

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: rs252944; hg19: chr5-160758337;