5-162092873-T-C

Variant names:

• chr5-162092873-T-C
• rs209358
• NM_198904.4:c.108-955T>C

Variant summary

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

The NM_198904.4(GABRG2):​c.108-955T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,954 control chromosomes in the GnomAD database, including 15,054 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 0.44 (15054 hom., cov: 32)
• Consequence: GABRG2 NM_198904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.689
• Publications: 5 publications found

Genes affected

GABRG2 (HGNC:4087): (gamma-aminobutyric acid type A receptor subunit gamma2) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammlian brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene have been associated with epilepsy and febrile seizures. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

GABRG2 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 74

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• febrile seizures, familial, 8

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Dravet syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• generalized epilepsy with febrile seizures plus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• self-limited epilepsy with centrotemporal spikes

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG2	NM_198904.4	c.108-955T>C		intron_variant	Intron 1 of 9	ENST00000639213.2	NP_944494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG2	ENST00000639213.2	c.108-955T>C		intron_variant	Intron 1 of 9	1	NM_198904.4	ENSP00000491909.2

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66946 AN: 151836 Hom.: 15031 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.441 AC: 67016 AN: 151954 Hom.: 15054 Cov.: 32 AF XY: 0.434 AC XY: 32185 AN XY: 74236

African (AFR) AF: 0.522 AC: 21638 AN: 41454

American (AMR) AF: 0.380 AC: 5798 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1504 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1677 AN: 5142

South Asian (SAS) AF: 0.354 AC: 1702 AN: 4814

European-Finnish (FIN) AF: 0.386 AC: 4075 AN: 10562

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.431 AC: 29274 AN: 67960

Other (OTH) AF: 0.405 AC: 852 AN: 2104

Alfa AF: 0.366 Hom.: 1546

Bravo AF: 0.440

Asia WGS AF: 0.349 AC: 1213 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.82
PhyloP100		-0.69
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: rs209358; hg19: chr5-161519879;