Variant chr9-98311161-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_005458.8(GABBR2):c.1938G>A(p.Glu646=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000674 in 1,613,920 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 10 hom. )

Consequence

GABBR2
NM_005458.8 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.21

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 9-98311161-C-T is Benign according to our data. Variant chr9-98311161-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 531172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.21 with no splicing effect.

BS2

High AC in GnomAd4 at 64 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GABBR2	NM_005458.8 linkuse as main transcript	c.1938G>A	p.Glu646=	synonymous_variant	14/19	ENST00000259455.4
GABBR2	XM_017015331.3 linkuse as main transcript	c.1644G>A	p.Glu548=	synonymous_variant	13/18
GABBR2	XM_005252316.6 linkuse as main transcript	c.1164G>A	p.Glu388=	synonymous_variant	12/17
GABBR2	XM_017015332.3 linkuse as main transcript	c.1164G>A	p.Glu388=	synonymous_variant	11/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GABBR2	ENST00000259455.4 linkuse as main transcript	c.1938G>A	p.Glu646=	synonymous_variant	14/19	1	NM_005458.8	P1
GABBR2	ENST00000634457.1 linkuse as main transcript	c.232-4816G>A		intron_variant		5
GABBR2	ENST00000635462.1 linkuse as main transcript	n.433G>A		non_coding_transcript_exon_variant	4/5	2
GABBR2	ENST00000637410.1 linkuse as main transcript	n.1716G>A		non_coding_transcript_exon_variant	14/19	5

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00119

AC:

298

AN:

251408

Hom.:

AF XY:

0.00152

AC XY:

207

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00679

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000449

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.000700

AC:

1023

AN:

1461626

Hom.:

Cov.:

AF XY:

0.000908

AC XY:

660

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00620

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000288

Gnomad4 OTH exome

AF:

0.000977

GnomAD4 genome

AF:

0.000420

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000550

Hom.:

Bravo

AF:

0.000276

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.000830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

GABBR2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.0

DANN

Benign

0.84

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