rs11949658

Variant names:

• chr5-161374717-G-A
• rs11949658
• NM_001371727.1:c.541+36258C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371727.1(GABRB2):​c.541+36258C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.081 in 152,136 control chromosomes in the GnomAD database, including 618 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 0.081 (618 hom., cov: 32)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 5 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):

• developmental and epileptic encephalopathy 92

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.541+36258C>T		intron_variant	Intron 5 of 9	ENST00000393959.6	NP_001358656.1
GABRB2	NM_021911.3	c.541+36258C>T		intron_variant	Intron 6 of 10		NP_068711.1
GABRB2	NM_000813.3	c.541+36258C>T		intron_variant	Intron 6 of 9		NP_000804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB2	ENST00000393959.6	c.541+36258C>T		intron_variant	Intron 5 of 9	1	NM_001371727.1	ENSP00000377531.1

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 12294 AN: 152018 Hom.: 610 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0542

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.0939

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.0810 AC: 12330 AN: 152136 Hom.: 618 Cov.: 32 AF XY: 0.0808 AC XY: 6011 AN XY: 74380

African (AFR) AF: 0.140 AC: 5806 AN: 41502

American (AMR) AF: 0.0541 AC: 826 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 102 AN: 3468

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5176

South Asian (SAS) AF: 0.0944 AC: 455 AN: 4820

European-Finnish (FIN) AF: 0.0695 AC: 736 AN: 10592

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0607 AC: 4124 AN: 67982

Other (OTH) AF: 0.0866 AC: 183 AN: 2112

Alfa AF: 0.0677 Hom.: 660

Bravo AF: 0.0819

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.68
DANN	Benign	0.22
PhyloP100		-0.0090
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: rs11949658; hg19: chr5-160801723;