5-162154029-T-A

Position:

• chr5-162154029-T-A

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.*661T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,596 control chromosomes in the GnomAD database, including 16,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (16062 hom., cov: 32)
  • Exomes 𝑓: 0.34 (40 hom.)
• Consequence: GABRG2 NM_198904.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91

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 5-162154029-T-A is Benign according to our data. Variant chr5-162154029-T-A is described in ClinVar as [Benign]. Clinvar id is 352656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABRG2	NM_198904.4	c.*661T>A		3_prime_UTR_variant	10/10	ENST00000639213.2	NP_944494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABRG2	ENST00000639213.2	c.*661T>A		3_prime_UTR_variant	10/10	1	NM_198904.4	ENSP00000491909	A1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68308 AN: 151870 Hom.: 16032 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.340 AC: 207 AN: 608 Hom.: 40 Cov.: 0 AF XY: 0.320 AC XY: 116 AN XY: 362

Gnomad4 AMR exome AF: 0.364

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.450 AC: 68391 AN: 151988 Hom.: 16062 Cov.: 32 AF XY: 0.451 AC XY: 33486 AN XY: 74270

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.408

Alfa AF: 0.431 Hom.: 1929

Bravo AF: 0.448

Asia WGS AF: 0.559 AC: 1937 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 13, 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	9.2
DANN	Benign	0.75

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: rs424740; hg19: chr5-161581035;