Variant rs35449008 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005458.8(GABBR2):c.483T>C(p.Pro161=) 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 462139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-98542020-A-G is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8 linkuse as main transcript	c.483T>C	p.Pro161=	synonymous_variant	3/19	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3 linkuse as main transcript	c.189T>C	p.Pro63=	synonymous_variant	2/18		XP_016870820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4 linkuse as main transcript	c.483T>C	p.Pro161=	synonymous_variant	3/19	1	NM_005458.8	ENSP00000259455	P1

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

GnomAD3 exomes

AF:

0.0339

AC:

8510

AN:

250898

Hom.:

294

AF XY:

0.0312

AC XY:

4236

AN XY:

135596

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 SAS exome

AF:

0.0104

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

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.0186

Gnomad4 ASJ exome

AF:

0.0208

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0109

Gnomad4 FIN exome

AF:

0.0335

Gnomad4 NFE exome

AF:

0.0339

Gnomad4 OTH exome

AF:

0.0355

GnomAD4 genome

AF:

0.0656

AC:

9988

AN:

152314

Hom.:

561

Cov.:

AF XY:

0.0645

AC XY:

4801

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.0322

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00683

Gnomad4 FIN

AF:

0.0369

Gnomad4 NFE

AF:

0.0333

Gnomad4 OTH

AF:

0.0468

Alfa

AF:

0.0479

Hom.:

217

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.1

DANN

Benign

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over