chr4-47320202-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000812.4(GABRB1):c.537C>A(p.Ile179Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,579,056 control chromosomes in the GnomAD database, including 29,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2389 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27253 hom. )

Consequence

GABRB1
NM_000812.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0820

Publications

13 publications found

Variant links:

Genes affected

GABRB1 (HGNC:4081): (gamma-aminobutyric acid type A receptor subunit beta1) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 1 subunit. It is mapped to chromosome 4p12 in a cluster comprised of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia. [provided by RefSeq, Jul 2008]

GABRB1 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 45
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

GABRB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 4-47320202-C-A is Benign according to our data. Variant chr4-47320202-C-A is described in ClinVar as Benign. ClinVar VariationId is 1573985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.082 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABRB1	NM_000812.4 link	c.537C>A	p.Ile179Ile	synonymous_variant	Exon 5 of 9	ENST00000295454.8	NP_000803.2	P18505-1X5DNL6
GABRB1	XM_024453976.2 link	c.438C>A	p.Ile146Ile	synonymous_variant	Exon 5 of 9		XP_024309744.1
GABRB1	XM_024453977.2 link	c.438C>A	p.Ile146Ile	synonymous_variant	Exon 6 of 10		XP_024309745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GABRB1	ENST00000295454.8 link	c.537C>A	p.Ile179Ile	synonymous_variant	Exon 5 of 9	1	NM_000812.4	ENSP00000295454.3	P18505-1
GABRB1	ENST00000510909.1 link	n.*205C>A		non_coding_transcript_exon_variant	Exon 4 of 5	4		ENSP00000426766.1	P18505-2
GABRB1	ENST00000510909.1 link	n.*205C>A		3_prime_UTR_variant	Exon 4 of 5	4		ENSP00000426766.1	P18505-2

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26172

AN:

152016

Hom.:

2392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.163

GnomAD2 exomes

AF:

0.170

AC:

42605

AN:

251052

AF XY:

0.170

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.128

Gnomad EAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.202

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.190

AC:

271421

AN:

1426922

Hom.:

27253

Cov.:

AF XY:

0.188

AC XY:

133974

AN XY:

712108

show subpopulations

African (AFR)

AF:

0.122

AC:

4005

AN:

32926

American (AMR)

AF:

0.131

AC:

5855

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

3310

AN:

25948

East Asian (EAS)

AF:

0.114

AC:

4502

AN:

39536

South Asian (SAS)

AF:

0.109

AC:

9336

AN:

85626

European-Finnish (FIN)

AF:

0.264

AC:

14082

AN:

53396

Middle Eastern (MID)

AF:

0.110

AC:

626

AN:

5716

European-Non Finnish (NFE)

AF:

0.203

AC:

219014

AN:

1079806

Other (OTH)

AF:

0.180

AC:

10691

AN:

59330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

9357

18715

28072

37430

46787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7358

14716

22074

29432

36790

<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:

0.172

AC:

26169

AN:

152134

Hom.:

2389

Cov.:

AF XY:

0.171

AC XY:

12724

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.127

AC:

5263

AN:

41502

American (AMR)

AF:

0.133

AC:

2037

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

443

AN:

3470

East Asian (EAS)

AF:

0.109

AC:

563

AN:

5178

South Asian (SAS)

AF:

0.115

AC:

554

AN:

4820

European-Finnish (FIN)

AF:

0.255

AC:

2701

AN:

10574

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14043

AN:

67994

Other (OTH)

AF:

0.162

AC:

342

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1120

2239

3359

4478

5598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<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:

0.189

Hom.:

12840

Bravo

AF:

0.158

Asia WGS

AF:

0.124

AC:

433

AN:

3478

EpiCase

AF:

0.194

EpiControl

AF:

0.196

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 28% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 26. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

6.9

(source)

DANN

Benign

0.81

PhyloP100

0.082

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over