rs12187676

Variant names:

• chr5-161539388-G-C
• rs12187676
• NM_001371727.1:c.237+5839C>G

Variant summary

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

The NM_001371727.1(GABRB2):​c.237+5839C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,082 control chromosomes in the GnomAD database, including 6,299 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 0.28 (6299 hom., cov: 32)
• Consequence: GABRB2 NM_001371727.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB2	NM_001371727.1	c.237+5839C>G		intron_variant	Intron 3 of 9	ENST00000393959.6	NP_001358656.1
GABRB2	NM_021911.3	c.237+5839C>G		intron_variant	Intron 4 of 10		NP_068711.1
GABRB2	NM_000813.3	c.237+5839C>G		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.237+5839C>G		intron_variant	Intron 3 of 9	1	NM_001371727.1	ENSP00000377531.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42027 AN: 151964 Hom.: 6284 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.277 AC: 42064 AN: 152082 Hom.: 6299 Cov.: 32 AF XY: 0.275 AC XY: 20441 AN XY: 74336

African (AFR) AF: 0.186 AC: 7725 AN: 41492

American (AMR) AF: 0.396 AC: 6053 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1477 AN: 5160

South Asian (SAS) AF: 0.264 AC: 1275 AN: 4822

European-Finnish (FIN) AF: 0.259 AC: 2735 AN: 10556

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21081 AN: 67970

Other (OTH) AF: 0.278 AC: 587 AN: 2114

Alfa AF: 0.290 Hom.: 851

Bravo AF: 0.283

Asia WGS AF: 0.287 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.62
DANN	Benign	0.46
PhyloP100		-1.1
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: rs12187676; hg19: chr5-160966394;