Genetic Variant ENST00000640757.1:c.109C>A (chr5-162036950-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

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

The ENST00000640757.1(GABRG2):c.109C>A(p.Pro37Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 152,296 control chromosomes in the GnomAD database, including 17,951 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.46 ( 17909 hom., cov: 32)

Exomes 𝑓: 0.49 ( 42 hom. )

Consequence

GABRG2
ENST00000640757.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0760

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012762249).

BP6

Variant 5-162036950-C-A is Benign according to our data. Variant chr5-162036950-C-A is described in ClinVar as [Benign]. Clinvar id is 3255256.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG2	ENST00000640757.1 link	c.109C>A	p.Pro37Thr	missense_variant	Exon 1 of 4	5		ENSP00000492329.1		A0A1W2PRM8
GABRG2	ENST00000639046.1 link	c.22+36722C>A		intron_variant	Intron 1 of 4	5		ENSP00000492659.1		A0A1W2PRU1

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

69964

AN:

151874

Hom.:

17904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.556

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.500

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.568

Gnomad OTH

AF:

0.436

GnomAD4 exome

AF:

0.493

AC:

150

AN:

304

Hom.:

Cov.:

AF XY:

0.470

AC XY:

110

AN XY:

234

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.417

Gnomad4 EAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.833

Gnomad4 NFE exome

AF:

0.508

Gnomad4 OTH exome

AF:

0.333

GnomAD4 genome

AF:

0.460

AC:

69979

AN:

151992

Hom.:

17909

Cov.:

AF XY:

0.465

AC XY:

34524

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.523

Gnomad4 ASJ

AF:

0.556

Gnomad4 EAS

AF:

0.319

Gnomad4 SAS

AF:

0.502

Gnomad4 FIN

AF:

0.627

Gnomad4 NFE

AF:

0.567

Gnomad4 OTH

AF:

0.431

Alfa

AF:

0.520

Hom.:

2701

Bravo

AF:

0.437

TwinsUK

AF:

0.575

AC:

2133

ALSPAC

AF:

0.569

AC:

2193

Asia WGS

AF:

0.398

AC:

1383

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 59. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.0

DANN

Benign

0.62

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0013

Splicing

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