rs418210

chr5-162153977-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198904.4(GABRG2):c.*609C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 153,912 control chromosomes in the GnomAD database, including 8,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8867 hom., cov: 32)
  • Exomes 𝑓: 0.22 (59 hom.)
• Consequence: GABRG2 NM_198904.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.665

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-162153977-C-T is Benign according to our data. Variant chr5-162153977-C-T is described in ClinVar as [Benign]. Clinvar id is 352655.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG2	NM_198904.4	c.*609C>T		3_prime_UTR_variant	10/10	ENST00000639213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG2	ENST00000639213.2	c.*609C>T		3_prime_UTR_variant	10/10	1	NM_198904.4	A1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48867 AN: 151788 Hom.: 8838 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.216 AC: 433 AN: 2006 Hom.: 59 Cov.: 0 AF XY: 0.217 AC XY: 227 AN XY: 1048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.322 AC: 48941 AN: 151906 Hom.: 8867 Cov.: 32 AF XY: 0.324 AC XY: 24014 AN XY: 74228

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.284

Alfa AF: 0.271 Hom.: 1468

Bravo AF: 0.323

Asia WGS AF: 0.350 AC: 1211 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epilepsy, childhood absence 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.26
Dann	Benign	0.56

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: rs418210; hg19: chr5-161580983; COSMIC: COSV62718144; COSMIC: COSV62718144;