rs252965

Variant names:

• chr5-161295856-G-T
• rs252965
• NM_001371727.1:c.1192-1428C>A

Variant summary

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

The NM_001371727.1(GABRB2):​c.1192-1428C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,186 control chromosomes in the GnomAD database, including 1,138 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 0.12 (1138 hom., cov: 33)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.535
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.1192-1428C>A		intron_variant	Intron 9 of 9	ENST00000393959.6	NP_001358656.1
GABRB2	NM_021911.3	c.1192-1428C>A		intron_variant	Intron 10 of 10		NP_068711.1
GABRB2	NM_000813.3	c.1078-1428C>A		intron_variant	Intron 9 of 9		NP_000804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRB2	ENST00000393959.6	c.1192-1428C>A		intron_variant	Intron 9 of 9	1	NM_001371727.1	ENSP00000377531.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17692 AN: 152068 Hom.: 1140 Cov.: 33

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0303

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.116 AC: 17687 AN: 152186 Hom.: 1138 Cov.: 33 AF XY: 0.115 AC XY: 8548 AN XY: 74408

African (AFR) AF: 0.0924 AC: 3837 AN: 41522

American (AMR) AF: 0.0818 AC: 1251 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3468

East Asian (EAS) AF: 0.0304 AC: 157 AN: 5170

South Asian (SAS) AF: 0.106 AC: 514 AN: 4830

European-Finnish (FIN) AF: 0.144 AC: 1526 AN: 10600

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9510 AN: 67990

Other (OTH) AF: 0.112 AC: 236 AN: 2110

Alfa AF: 0.132 Hom.: 2145

Bravo AF: 0.110

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.44
DANN	Benign	0.56
PhyloP100		-0.54
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: rs252965; hg19: chr5-160722863;