dbSNP rs1864797: GABRG3:c.270+46466T>A (chr15-27073287-T-A) – 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.270+46466T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,220 control chromosomes in the GnomAD database, including 3,399 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 0.21 ( 3399 hom., cov: 33)

Consequence

GABRG3
NM_033223.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.110

Publications

0 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:

GABRG3-AS1 (HGNC:40249): (GABRG3 antisense RNA 1)

GABRG3-AS1 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5 link	c.270+46466T>A		intron_variant	Intron 3 of 9	ENST00000615808.5	NP_150092.2	Q99928-1
GABRG3	NM_001270873.2 link	c.270+46466T>A		intron_variant	Intron 3 of 5		NP_001257802.1	Q99928-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GABRG3	ENST00000615808.5 link	c.270+46466T>A	intron_variant	Intron 3 of 9	1	NM_033223.5	ENSP00000479113.1	Q99928-1
GABRG3	ENST00000555083.5 link	c.270+46466T>A	intron_variant	Intron 3 of 5	2		ENSP00000452244.1	Q99928-2
GABRG3-AS1	ENST00000660679.1 link	n.376+27536A>T	intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31375

AN:

152102

Hom.:

3387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.0767

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.206

AC:

31419

AN:

152220

Hom.:

3399

Cov.:

AF XY:

0.201

AC XY:

14935

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.258

AC:

10711

AN:

41524

American (AMR)

AF:

0.157

AC:

2397

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

761

AN:

3470

East Asian (EAS)

AF:

0.117

AC:

603

AN:

5174

South Asian (SAS)

AF:

0.0770

AC:

372

AN:

4830

European-Finnish (FIN)

AF:

0.154

AC:

1636

AN:

10616

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14203

AN:

67994

Other (OTH)

AF:

0.207

AC:

437

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1299

2598

3897

5196

6495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.217

Hom.:

439

Bravo

AF:

0.211

Asia WGS

AF:

0.123

AC:

429

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.5

(source)

DANN

Benign

0.75

PhyloP100

0.11

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