5-162071731-T-C

Variant names:

• chr5-162071731-T-C
• rs183294
• NM_198904.4:c.107+3625T>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.107+3625T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,650 control chromosomes in the GnomAD database, including 28,802 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 0.62 (28802 hom., cov: 31)
• Consequence: GABRG2 NM_198904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953
• Publications: 9 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: G2P, Ambry Genetics, 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.641 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG2	NM_198904.4	MANE Select	c.107+3625T>C		intron	N/A	NP_944494.1	P18507-2
	GABRG2	NM_198903.2		c.107+3625T>C		intron	N/A	NP_944493.2	P18507-3
	GABRG2	NM_001375343.1		c.107+3625T>C		intron	N/A	NP_001362272.1	A0A1X7SBZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRG2	ENST00000639213.2	TSL:1 MANE Select	c.107+3625T>C		intron	N/A	ENSP00000491909.2	P18507-2
	GABRG2	ENST00000414552.6	TSL:1	c.107+3625T>C		intron	N/A	ENSP00000410732.2	P18507-3
	GABRG2	ENST00000639111.2	TSL:1	c.107+3625T>C		intron	N/A	ENSP00000492125.2	P18507-1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93219 AN: 151532 Hom.: 28765 Cov.: 31

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.615 AC: 93308 AN: 151650 Hom.: 28802 Cov.: 31 AF XY: 0.612 AC XY: 45364 AN XY: 74104

African (AFR) AF: 0.579 AC: 23969 AN: 41396

American (AMR) AF: 0.652 AC: 9932 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1933 AN: 3466

East Asian (EAS) AF: 0.635 AC: 3268 AN: 5146

South Asian (SAS) AF: 0.650 AC: 3131 AN: 4818

European-Finnish (FIN) AF: 0.609 AC: 6424 AN: 10548

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42677 AN: 67734

Other (OTH) AF: 0.585 AC: 1233 AN: 2108

Alfa AF: 0.621 Hom.: 46649

Bravo AF: 0.613

Asia WGS AF: 0.682 AC: 2372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.35
PhyloP100		-0.95
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: rs183294; hg19: chr5-161498737;