chr5-162088209-C-T

Position:

• chr5-162088209-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198904.4(GABRG2):​c.108-5619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,038 control chromosomes in the GnomAD database, including 1,028 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 0.11 (1028 hom., cov: 32)
• Consequence: GABRG2 NM_198904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG2	NM_198904.4	c.108-5619C>T		intron_variant		ENST00000639213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG2	ENST00000639213.2	c.108-5619C>T		intron_variant		1	NM_198904.4	A1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17050 AN: 151920 Hom.: 1029 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0777

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0979

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.112 AC: 17058 AN: 152038 Hom.: 1028 Cov.: 32 AF XY: 0.110 AC XY: 8209 AN XY: 74294

Gnomad4 AFR AF: 0.0855

Gnomad4 AMR AF: 0.0886

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0777

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0979

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.121

Alfa AF: 0.132 Hom.: 1833

Bravo AF: 0.111

Asia WGS AF: 0.114 AC: 397 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	0.27
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2268582; hg19: chr5-161515215; COSMIC: COSV62716375;