dbSNP rs976156: GABRG1:p.Thr88Thr (chr4-46084043-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_173536.4(GABRG1):c.264A>G(p.Thr88Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,563,678 control chromosomes in the GnomAD database, including 242,916 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 0.58 ( 26452 hom., cov: 31)

Exomes 𝑓: 0.55 ( 216464 hom. )

Consequence

GABRG1
NM_173536.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

25 publications found

Variant links:

Genes affected

GABRG1 (HGNC:4086): (gamma-aminobutyric acid type A receptor subunit gamma1) The protein encoded by this gene belongs to the ligand-gated ionic channel family. It is an integral membrane protein and plays an important role in inhibiting neurotransmission by binding to the benzodiazepine receptor and opening an integral chloride channel. This gene is clustered with three other family members on chromosome 4. [provided by RefSeq, Jul 2008]

GABRG1 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: LIMITED Submitted by: G2P

GABRG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP7

Synonymous conserved (PhyloP=-1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4 link	c.264A>G	p.Thr88Thr	synonymous_variant	Exon 3 of 9	ENST00000295452.5	NP_775807.2	Q8N1C3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5 link	c.264A>G	p.Thr88Thr	synonymous_variant	Exon 3 of 9	1	NM_173536.4	ENSP00000295452.4		Q8N1C3

Frequencies

GnomAD3 genomes

AF:

0.583

AC:

88121

AN:

151172

Hom.:

26409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.664

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.359

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.548

GnomAD2 exomes

AF:

0.515

AC:

115648

AN:

224378

AF XY:

0.504

show subpopulations

Gnomad AFR exome

AF:

0.697

Gnomad AMR exome

AF:

0.533

Gnomad ASJ exome

AF:

0.433

Gnomad EAS exome

AF:

0.367

Gnomad FIN exome

AF:

0.633

Gnomad NFE exome

AF:

0.546

Gnomad OTH exome

AF:

0.505

GnomAD4 exome

AF:

0.547

AC:

772281

AN:

1412388

Hom.:

216464

Cov.:

AF XY:

0.539

AC XY:

379010

AN XY:

703114

show subpopulations

African (AFR)

AF:

0.692

AC:

22142

AN:

31984

American (AMR)

AF:

0.536

AC:

22869

AN:

42692

Ashkenazi Jewish (ASJ)

AF:

0.443

AC:

11240

AN:

25354

East Asian (EAS)

AF:

0.323

AC:

12466

AN:

38642

South Asian (SAS)

AF:

0.344

AC:

28655

AN:

83348

European-Finnish (FIN)

AF:

0.632

AC:

32983

AN:

52210

Middle Eastern (MID)

AF:

0.324

AC:

1835

AN:

5658

European-Non Finnish (NFE)

AF:

0.566

AC:

608400

AN:

1074066

Other (OTH)

AF:

0.542

AC:

31691

AN:

58434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

14124

28248

42371

56495

70619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16862

33724

50586

67448

84310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.583

AC:

88233

AN:

151290

Hom.:

26452

Cov.:

AF XY:

0.579

AC XY:

42810

AN XY:

73882

show subpopulations

African (AFR)

AF:

0.691

AC:

28585

AN:

41346

American (AMR)

AF:

0.546

AC:

8234

AN:

15082

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

1466

AN:

3452

East Asian (EAS)

AF:

0.360

AC:

1853

AN:

5152

South Asian (SAS)

AF:

0.337

AC:

1620

AN:

4806

European-Finnish (FIN)

AF:

0.641

AC:

6778

AN:

10572

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.560

AC:

37841

AN:

67580

Other (OTH)

AF:

0.545

AC:

1144

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1775

3550

5324

7099

8874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

730

1460

2190

2920

3650

<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:

0.558

Hom.:

72706

Bravo

AF:

0.584

Asia WGS

AF:

0.395

AC:

1375

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.1

(source)

DANN

Benign

0.58

PhyloP100

-1.0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over