Variant 5-162153977-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000639213.2(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
ENST00000639213.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.665

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
GABRG2	NM_198904.4 linkuse as main transcript	c.*609C>T		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 linkuse as main transcript	c.*609C>T		3_prime_UTR_variant	10/10	1	NM_198904.4	ENSP00000491909	A1	P18507-2

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48867

AN:

151788

Hom.:

8838

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.217

AC XY:

227

AN XY:

1048

show subpopulations

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.:

AF XY:

0.324

AC XY:

24014

AN XY:

74228

show subpopulations

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over