NM_005458.8:c.483T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005458.8(GABBR2):c.483T>C(p.Pro161Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 1,614,052 control chromosomes in the GnomAD database, including 1,772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 561 hom., cov: 33)

Exomes 𝑓: 0.034 ( 1211 hom. )

Consequence

GABBR2
NM_005458.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.664

Publications

4 publications found

Variant links:

Genes affected

GABBR2 (HGNC:4507): (gamma-aminobutyric acid type B receptor subunit 2) The multi-pass membrane protein encoded by this gene belongs to the G-protein coupled receptor 3 family and GABA-B receptor subfamily. The GABA-B receptors inhibit neuronal activity through G protein-coupled second-messenger systems, which regulate the release of neurotransmitters, and the activity of ion channels and adenylyl cyclase. This receptor subunit forms an active heterodimeric complex with GABA-B receptor subunit 1, neither of which is effective on its own. Allelic variants of this gene have been associated with nicotine dependence.[provided by RefSeq, Jan 2010]

GABBR2 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 59
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder with poor language and loss of hand skills
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
atypical Rett syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GABBR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 9-98542020-A-G is Benign according to our data. Variant chr9-98542020-A-G is described in ClinVar as Benign. ClinVar VariationId is 462139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.664 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005458.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR2	NM_005458.8	MANE Select	c.483T>C	p.Pro161Pro	synonymous	Exon 3 of 19	NP_005449.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GABBR2	ENST00000259455.4	TSL:1 MANE Select	c.483T>C	p.Pro161Pro	synonymous	Exon 3 of 19	ENSP00000259455.2
GABBR2	ENST00000637717.1	TSL:5	c.99T>C	p.Pro33Pro	synonymous	Exon 3 of 3	ENSP00000490789.1
GABBR2	ENST00000477471.1	TSL:3	n.270T>C		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.0655

AC:

9963

AN:

152196

Hom.:

559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0323

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00682

Gnomad FIN

AF:

0.0369

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0333

Gnomad OTH

AF:

0.0473

GnomAD2 exomes

AF:

0.0339

AC:

8510

AN:

250898

AF XY:

0.0312

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.0174

Gnomad ASJ exome

AF:

0.0203

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0336

Gnomad NFE exome

AF:

0.0346

Gnomad OTH exome

AF:

0.0259

GnomAD4 exome

AF:

0.0338

AC:

49468

AN:

1461738

Hom.:

1211

Cov.:

AF XY:

0.0329

AC XY:

23903

AN XY:

727170

show subpopulations

African (AFR)

AF:

0.159

AC:

5335

AN:

33474

American (AMR)

AF:

0.0186

AC:

831

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0208

AC:

543

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.0109

AC:

938

AN:

86248

European-Finnish (FIN)

AF:

0.0335

AC:

1791

AN:

53416

Middle Eastern (MID)

AF:

0.0250

AC:

144

AN:

5768

European-Non Finnish (NFE)

AF:

0.0339

AC:

37743

AN:

1111906

Other (OTH)

AF:

0.0355

AC:

2143

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

2423

4845

7268

9690

12113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1438

2876

4314

5752

7190

<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:

0.0656

AC:

9988

AN:

152314

Hom.:

561

Cov.:

AF XY:

0.0645

AC XY:

4801

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.159

AC:

6618

AN:

41540

American (AMR)

AF:

0.0322

AC:

493

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00683

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0369

AC:

392

AN:

10614

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0333

AC:

2267

AN:

68040

Other (OTH)

AF:

0.0468

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

456

912

1367

1823

2279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

208

312

416

520

<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:

0.0468

Hom.:

609

Bravo

AF:

0.0697

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0297

EpiControl

AF:

0.0295

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

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Epileptic encephalopathy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.1

(source)

DANN

Benign

0.72

PhyloP100

-0.66

Mutation Taster

=90/10

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over