dbSNP rs2061051: GABRG3:c.271-51145G>A (chr15-27275664-G-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.271-51145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,042 control chromosomes in the GnomAD database, including 31,291 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 0.63 ( 31291 hom., cov: 33)

Consequence

GABRG3
NM_033223.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0300

Publications

6 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:

Genome browser will be placed here

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=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG3	NM_033223.5 link	c.271-51145G>A		intron_variant	Intron 3 of 9	ENST00000615808.5	NP_150092.2	Q99928-1
GABRG3	NM_001270873.2 link	c.271-51145G>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.271-51145G>A	intron_variant	Intron 3 of 9	1	NM_033223.5	ENSP00000479113.1	Q99928-1
GABRG3	ENST00000554696.5 link	c.96+4027G>A	intron_variant	Intron 1 of 5	3		ENSP00000451862.1	H0YJP1
GABRG3	ENST00000555083.5 link	c.271-51145G>A	intron_variant	Intron 3 of 5	2		ENSP00000452244.1	Q99928-2
GABRG3	ENST00000554786.1 link	n.97+4027G>A	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96309

AN:

151926

Hom.:

31258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.707

Gnomad AMI

AF:

0.693

Gnomad AMR

AF:

0.561

Gnomad ASJ

AF:

0.496

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.649

Gnomad OTH

AF:

0.569

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

GnomAD4 genome

AF:

0.634

AC:

96388

AN:

152042

Hom.:

31291

Cov.:

AF XY:

0.629

AC XY:

46729

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.707

AC:

29345

AN:

41488

American (AMR)

AF:

0.562

AC:

8579

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

1720

AN:

3470

East Asian (EAS)

AF:

0.288

AC:

1484

AN:

5152

South Asian (SAS)

AF:

0.446

AC:

2141

AN:

4804

European-Finnish (FIN)

AF:

0.668

AC:

7058

AN:

10560

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.649

AC:

44090

AN:

67972

Other (OTH)

AF:

0.561

AC:

1187

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1751

3502

5253

7004

8755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

762

1524

2286

3048

3810

<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:

0.639

Hom.:

52367

Bravo

AF:

0.631

Asia WGS

AF:

0.366

AC:

1271

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.85

(source)

DANN

Benign

0.30

PhyloP100

-0.030

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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