rs2962407

Variant names:

• chr5-161481189-A-G
• rs2962407
• NM_001371727.1:c.238-21345T>C

Variant summary

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

The NM_001371727.1(GABRB2):​c.238-21345T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,824 control chromosomes in the GnomAD database, including 28,077 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 0.59 (28077 hom., cov: 32)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 0 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.238-21345T>C		intron_variant	Intron 3 of 9	ENST00000393959.6	NP_001358656.1
GABRB2	NM_021911.3	c.238-21345T>C		intron_variant	Intron 4 of 10		NP_068711.1
GABRB2	NM_000813.3	c.238-21345T>C		intron_variant	Intron 4 of 9		NP_000804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB2	ENST00000393959.6	c.238-21345T>C		intron_variant	Intron 3 of 9	1	NM_001371727.1	ENSP00000377531.1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89558 AN: 151704 Hom.: 28065 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.590 AC: 89597 AN: 151824 Hom.: 28077 Cov.: 32 AF XY: 0.593 AC XY: 43975 AN XY: 74150

African (AFR) AF: 0.360 AC: 14918 AN: 41438

American (AMR) AF: 0.622 AC: 9468 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2464 AN: 3468

East Asian (EAS) AF: 0.575 AC: 2945 AN: 5124

South Asian (SAS) AF: 0.739 AC: 3557 AN: 4812

European-Finnish (FIN) AF: 0.672 AC: 7086 AN: 10546

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47149 AN: 67904

Other (OTH) AF: 0.592 AC: 1248 AN: 2108

Alfa AF: 0.653 Hom.: 86497

Bravo AF: 0.571

Asia WGS AF: 0.647 AC: 2249 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.83
PhyloP100		-0.012
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: rs2962407; hg19: chr5-160908195; COSMIC: COSV50905563;