chr5-162090053-C-T

Position:

• chr5-162090053-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.108-3775C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,920 control chromosomes in the GnomAD database, including 23,169 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 0.55 (23169 hom., cov: 32)
• Consequence: GABRG2 NM_198904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG2	NM_198904.4	c.108-3775C>T		intron_variant		ENST00000639213.2	NP_944494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG2	ENST00000639213.2	c.108-3775C>T		intron_variant		1	NM_198904.4	ENSP00000491909.2

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83388 AN: 151802 Hom.: 23143 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.549 AC: 83464 AN: 151920 Hom.: 23169 Cov.: 32 AF XY: 0.540 AC XY: 40107 AN XY: 74226

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.524

Alfa AF: 0.554 Hom.: 30373

Bravo AF: 0.546

Asia WGS AF: 0.463 AC: 1608 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.83
DANN	Benign	0.15

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: rs209353; hg19: chr5-161517059;