rs252944

Variant names:

• chr5-161331330-C-G
• rs252944
• NM_001371727.1:c.833-203G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy 92

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371727.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	NM_001371727.1	MANE Select	c.833-203G>C		intron	N/A	NP_001358656.1	P47870-2
	GABRB2	NM_021911.3		c.833-203G>C		intron	N/A	NP_068711.1	P47870-2
	GABRB2	NM_000813.3		c.833-203G>C		intron	N/A	NP_000804.1	P47870-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	ENST00000393959.6	TSL:1 MANE Select	c.833-203G>C		intron	N/A	ENSP00000377531.1	P47870-2
	GABRB2	ENST00000353437.10	TSL:1	c.833-203G>C		intron	N/A	ENSP00000274546.6	P47870-1
	GABRB2	ENST00000520240.5	TSL:1	c.833-203G>C		intron	N/A	ENSP00000429320.1	P47870-1

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

African (AFR) AF: 0.131 AC: 5442 AN: 41466

American (AMR) AF: 0.163 AC: 2495 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 441 AN: 3470

East Asian (EAS) AF: 0.167 AC: 863 AN: 5154

South Asian (SAS) AF: 0.160 AC: 771 AN: 4816

European-Finnish (FIN) AF: 0.129 AC: 1356 AN: 10552

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9246 AN: 67980

Other (OTH) AF: 0.111 AC: 235 AN: 2112

Alfa AF: 0.141 Hom.: 196

Bravo AF: 0.140

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.11
DANN	Benign	0.40
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs252944; hg19: chr5-160758337;