rs169793

Variant names:

• chr5-162114029-T-A
• rs169793
• NM_198904.4:c.769+10003T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-162114029-T-A
• chr5-162114029-T-C
• chr5-162114029-T-G

Variant summary

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

The NM_198904.4(GABRG2):​c.769+10003T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,084 control chromosomes in the GnomAD database, including 26,963 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 (26963 hom., cov: 32)
• Consequence: GABRG2 NM_198904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198904.4. 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
	GABRG2	NM_198904.4	MANE Select	c.769+10003T>A		intron	N/A	NP_944494.1
	GABRG2	NM_198903.2		c.889+10003T>A		intron	N/A	NP_944493.2
	GABRG2	NM_001375343.1		c.889+10003T>A		intron	N/A	NP_001362272.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG2	ENST00000639213.2	TSL:1 MANE Select	c.769+10003T>A		intron	N/A	ENSP00000491909.2
	GABRG2	ENST00000414552.6	TSL:1	c.889+10003T>A		intron	N/A	ENSP00000410732.2
	GABRG2	ENST00000639111.2	TSL:1	c.769+10003T>A		intron	N/A	ENSP00000492125.2

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90040 AN: 151966 Hom.: 26949 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.592 AC: 90088 AN: 152084 Hom.: 26963 Cov.: 32 AF XY: 0.589 AC XY: 43785 AN XY: 74312

African (AFR) AF: 0.661 AC: 27429 AN: 41498

American (AMR) AF: 0.547 AC: 8356 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1889 AN: 3468

East Asian (EAS) AF: 0.393 AC: 2032 AN: 5170

South Asian (SAS) AF: 0.487 AC: 2349 AN: 4822

European-Finnish (FIN) AF: 0.590 AC: 6230 AN: 10554

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.587 AC: 39882 AN: 67982

Other (OTH) AF: 0.605 AC: 1278 AN: 2114

Alfa AF: 0.485 Hom.: 1430

Bravo AF: 0.594

Asia WGS AF: 0.439 AC: 1526 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.40
PhyloP100		0.093
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: rs169793; hg19: chr5-161541035; COSMIC: COSV62716471;