Variant 15-27480771-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_033223.5(GABRG3):c.696C>T(p.Ile232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00868 in 1,613,704 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0088 ( 109 hom. )

Consequence

GABRG3
NM_033223.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.736

Variant links:

Genes affected

GABRG3 (HGNC:4088): (gamma-aminobutyric acid type A receptor subunit gamma3) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. The protein encoded by this gene is a gamma subunit, which contains the benzodiazepine binding site. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

GABRG3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 15-27480771-C-T is Benign according to our data. Variant chr15-27480771-C-T is described in ClinVar as [Benign]. Clinvar id is 778095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.736 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00884 (12919/1461412) while in subpopulation MID AF= 0.0187 (108/5768). AF 95% confidence interval is 0.0159. There are 109 homozygotes in gnomad4_exome. There are 6369 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG3	NM_033223.5 linkuse as main transcript	c.696C>T	p.Ile232=	synonymous_variant	6/10	ENST00000615808.5
GABRG3	NM_001270873.2 linkuse as main transcript	c.696C>T	p.Ile232=	synonymous_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG3	ENST00000615808.5 linkuse as main transcript	c.696C>T	p.Ile232=	synonymous_variant	6/10	1	NM_033223.5	P1	Q99928-1
GABRG3	ENST00000333743.10 linkuse as main transcript	c.159C>T	p.Ile53=	synonymous_variant	3/7	5
GABRG3	ENST00000554696.5 linkuse as main transcript	c.522C>T	p.Ile174=	synonymous_variant	4/6	3
GABRG3	ENST00000555083.5 linkuse as main transcript	c.696C>T	p.Ile232=	synonymous_variant	6/6	2			Q99928-2

Frequencies

GnomAD3 genomes

AF:

0.00721

AC:

1097

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00415

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00907

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.00874

AC:

2171

AN:

248458

Hom.:

AF XY:

0.00872

AC XY:

1175

AN XY:

134786

show subpopulations

Gnomad AFR exome

AF:

0.00143

Gnomad AMR exome

AF:

0.00389

Gnomad ASJ exome

AF:

0.0562

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.00233

Gnomad FIN exome

AF:

0.00349

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.00884

AC:

12919

AN:

1461412

Hom.:

109

Cov.:

AF XY:

0.00876

AC XY:

6369

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.00215

Gnomad4 AMR exome

AF:

0.00394

Gnomad4 ASJ exome

AF:

0.0549

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.00254

Gnomad4 FIN exome

AF:

0.00358

Gnomad4 NFE exome

AF:

0.00907

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00719

AC:

1095

AN:

152292

Hom.:

Cov.:

AF XY:

0.00694

AC XY:

517

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00204

Gnomad4 AMR

AF:

0.00784

Gnomad4 ASJ

AF:

0.0539

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00415

Gnomad4 NFE

AF:

0.00906

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.00782

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0116

EpiControl

AF:

0.0119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

6.3

DANN

Benign

0.89

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