5-162103379-T-C

Position:

• chr5-162103379-T-C

Variant summary

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

The NM_198904.4(GABRG2):​c.632-510T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 158,236 control chromosomes in the GnomAD database, including 38,637 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 0.70 (37103 hom., cov: 33)
  • Exomes 𝑓: 0.70 (1534 hom.)
• Consequence: GABRG2 NM_198904.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG2	NM_198904.4	c.632-510T>C		intron_variant		ENST00000639213.2	NP_944494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG2	ENST00000639213.2	c.632-510T>C		intron_variant		1	NM_198904.4	ENSP00000491909.2

Frequencies

GnomAD3 genomes AF: 0.697 AC: 106024 AN: 152022 Hom.: 37086 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.696

GnomAD4 exome AF: 0.698 AC: 4257 AN: 6096 Hom.: 1534 Cov.: 0 AF XY: 0.704 AC XY: 2229 AN XY: 3164

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.772

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.564

Gnomad4 SAS exome AF: 0.734

Gnomad4 FIN exome AF: 0.672

Gnomad4 NFE exome AF: 0.677

Gnomad4 OTH exome AF: 0.677

GnomAD4 genome AF: 0.697 AC: 106085 AN: 152140 Hom.: 37103 Cov.: 33 AF XY: 0.700 AC XY: 52073 AN XY: 74348

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.753

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.699

Alfa AF: 0.698 Hom.: 4623

Bravo AF: 0.701

Asia WGS AF: 0.724 AC: 2516 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.78

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: rs211032; hg19: chr5-161530385; COSMIC: COSV62716427; COSMIC: COSV62716427;