Genetic Variant NM_173536.4:c.*60G>A (chr4-46040928-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_173536.4(GABRG1):c.*60G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,486,312 control chromosomes in the GnomAD database, including 165,779 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 0.50 ( 19826 hom., cov: 32)

Exomes 𝑓: 0.46 ( 145953 hom. )

Consequence

GABRG1
NM_173536.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.09

Publications

10 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRG1	NM_173536.4 link	c.*60G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000295452.5	NP_775807.2
GABRG1	XM_017007990.2 link	c.*60G>A		3_prime_UTR_variant	Exon 7 of 7		XP_016863479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABRG1	ENST00000295452.5 link	c.*60G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_173536.4	ENSP00000295452.4

Frequencies

GnomAD3 genomes

AF:

0.504

AC:

76354

AN:

151608

Hom.:

19792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.619

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.472

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.343

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.474

GnomAD4 exome

AF:

0.464

AC:

618645

AN:

1334584

Hom.:

145953

Cov.:

AF XY:

0.458

AC XY:

303824

AN XY:

662836

show subpopulations

African (AFR)

AF:

0.623

AC:

18411

AN:

29568

American (AMR)

AF:

0.486

AC:

16574

AN:

34082

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

9319

AN:

21662

East Asian (EAS)

AF:

0.325

AC:

12668

AN:

38938

South Asian (SAS)

AF:

0.337

AC:

24636

AN:

73184

European-Finnish (FIN)

AF:

0.541

AC:

26580

AN:

49106

Middle Eastern (MID)

AF:

0.300

AC:

1548

AN:

5168

European-Non Finnish (NFE)

AF:

0.470

AC:

482754

AN:

1027432

Other (OTH)

AF:

0.472

AC:

26155

AN:

55444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

15538

31076

46615

62153

77691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14402

28804

43206

57608

72010

<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:

0.504

AC:

76458

AN:

151728

Hom.:

19826

Cov.:

AF XY:

0.503

AC XY:

37295

AN XY:

74132

show subpopulations

African (AFR)

AF:

0.619

AC:

25651

AN:

41424

American (AMR)

AF:

0.473

AC:

7175

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1462

AN:

3468

East Asian (EAS)

AF:

0.359

AC:

1846

AN:

5146

South Asian (SAS)

AF:

0.329

AC:

1585

AN:

4822

European-Finnish (FIN)

AF:

0.556

AC:

5856

AN:

10538

Middle Eastern (MID)

AF:

0.339

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.461

AC:

31277

AN:

67836

Other (OTH)

AF:

0.472

AC:

993

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1958

3915

5873

7830

9788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

670

1340

2010

2680

3350

<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:

0.488

Hom.:

5137

Bravo

AF:

0.505

Asia WGS

AF:

0.393

AC:

1367

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.35

(source)

DANN

Benign

0.39

PhyloP100

-2.1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over