Variant rs34701111 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.2619A>G(p.Arg873=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,610,204 control chromosomes in the GnomAD database, including 3,332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 1826 hom., cov: 33)

Exomes 𝑓: 0.0080 ( 1506 hom. )

Consequence

GABBR2
NM_005458.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.97

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=-0.54).

BP6

Variant 9-98293826-T-C is Benign according to our data. Variant chr9-98293826-T-C is described in ClinVar as [Benign]. Clinvar id is 462133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GABBR2	NM_005458.8 linkuse as main transcript	c.2619A>G	p.Arg873=	synonymous_variant	18/19	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3 linkuse as main transcript	c.2325A>G	p.Arg775=	synonymous_variant	17/18		XP_016870820.1
GABBR2	XM_005252316.6 linkuse as main transcript	c.1845A>G	p.Arg615=	synonymous_variant	16/17		XP_005252373.1
GABBR2	XM_017015332.3 linkuse as main transcript	c.1845A>G	p.Arg615=	synonymous_variant	15/16		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4 linkuse as main transcript	c.2619A>G	p.Arg873=	synonymous_variant	18/19	1	NM_005458.8	ENSP00000259455	P1
GABBR2	ENST00000637410.1 linkuse as main transcript	n.2397A>G		non_coding_transcript_exon_variant	18/19	5

Frequencies

GnomAD3 genomes

AF:

0.0841

AC:

12801

AN:

152180

Hom.:

1826

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0284

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.0583

GnomAD3 exomes

AF:

0.0214

AC:

5391

AN:

251330

Hom.:

702

AF XY:

0.0155

AC XY:

2110

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.299

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000677

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.00802

AC:

11691

AN:

1457906

Hom.:

1506

Cov.:

AF XY:

0.00682

AC XY:

4950

AN XY:

725676

show subpopulations

Gnomad4 AFR exome

AF:

0.291

Gnomad4 AMR exome

AF:

0.0134

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000627

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000324

Gnomad4 OTH exome

AF:

0.0177

GnomAD4 genome

AF:

0.0842

AC:

12818

AN:

152298

Hom.:

1826

Cov.:

AF XY:

0.0808

AC XY:

6022

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.294

Gnomad4 AMR

AF:

0.0284

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.0577

Alfa

AF:

0.0492

Hom.:

532

Bravo

AF:

0.0973

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.000873

EpiControl

AF:

0.00113

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 17, 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

-0.54

CADD

Benign

8.1

DANN

Benign

0.67

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