dbSNP rs968671: GABRG3:c.271-118048A>G (chr15-27208761-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033223.5(GABRG3):c.271-118048A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 152,408 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.034 ( 168 hom., cov: 33)

Exomes 𝑓: 0.011 ( 0 hom. )

Consequence

GABRG3
NM_033223.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.324

Publications

1 publications found

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:

ENSG00000214254 (HGNC:):

ENSG00000214254 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5 link	c.271-118048A>G		intron_variant	Intron 3 of 9	ENST00000615808.5	NP_150092.2
GABRG3	NM_001270873.2 link	c.271-118048A>G		intron_variant	Intron 3 of 5		NP_001257802.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
GABRG3	ENST00000615808.5 link	c.271-118048A>G	intron_variant	Intron 3 of 9	1	NM_033223.5	ENSP00000479113.1
GABRG3	ENST00000555083.5 link	c.271-118048A>G	intron_variant	Intron 3 of 5	2		ENSP00000452244.1
ENSG00000214254	ENST00000438334.1 link	n.-126T>C	upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0341

AC:

5184

AN:

152116

Hom.:

168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0816

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.00540

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0169

Gnomad OTH

AF:

0.0349

GnomAD4 exome

AF:

0.0115

AC:

AN:

174

Hom.:

AF XY:

0.0111

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0154

AC:

AN:

130

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0342

AC:

5203

AN:

152234

Hom.:

168

Cov.:

AF XY:

0.0329

AC XY:

2448

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0817

AC:

3395

AN:

41540

American (AMR)

AF:

0.0157

AC:

240

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3470

East Asian (EAS)

AF:

0.00541

AC:

AN:

5176

South Asian (SAS)

AF:

0.0185

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0127

AC:

135

AN:

10604

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0169

AC:

1151

AN:

68008

Other (OTH)

AF:

0.0346

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

238

476

714

952

1190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0267

Hom.:

161

Bravo

AF:

0.0351

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.84

(source)

DANN

Benign

0.48

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over