rs92516

Variant names:

• chr5-161313192-C-A
• rs92516
• NM_001371727.1:c.1191+13176G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-161313192-C-A
• chr5-161313192-C-T

Variant summary

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

The ENST00000393959.6(GABRB2):​c.1191+13176G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,914 control chromosomes in the GnomAD database, including 21,596 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 0.50 (21596 hom., cov: 31)
• Consequence: GABRB2 ENST00000393959.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393959.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	NM_001371727.1	MANE Select	c.1191+13176G>T		intron	N/A	NP_001358656.1
	GABRB2	NM_021911.3		c.1191+13176G>T		intron	N/A	NP_068711.1
	GABRB2	NM_000813.3		c.1077+17691G>T		intron	N/A	NP_000804.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB2	ENST00000393959.6	TSL:1 MANE Select	c.1191+13176G>T		intron	N/A	ENSP00000377531.1
	GABRB2	ENST00000353437.10	TSL:1	c.1077+17691G>T		intron	N/A	ENSP00000274546.6
	GABRB2	ENST00000520240.5	TSL:1	c.1077+17691G>T		intron	N/A	ENSP00000429320.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76500 AN: 151796 Hom.: 21551 Cov.: 31

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.504 AC: 76597 AN: 151914 Hom.: 21596 Cov.: 31 AF XY: 0.506 AC XY: 37532 AN XY: 74242

African (AFR) AF: 0.764 AC: 31656 AN: 41460

American (AMR) AF: 0.541 AC: 8249 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1159 AN: 3468

East Asian (EAS) AF: 0.458 AC: 2360 AN: 5154

South Asian (SAS) AF: 0.380 AC: 1827 AN: 4814

European-Finnish (FIN) AF: 0.468 AC: 4926 AN: 10528

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24922 AN: 67930

Other (OTH) AF: 0.488 AC: 1033 AN: 2116

Alfa AF: 0.408 Hom.: 8051

Bravo AF: 0.527

Asia WGS AF: 0.444 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.65
DANN	Benign	0.48
PhyloP100		-0.34
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: rs92516; hg19: chr5-160740199;