rs35449008

chr9-98542020-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.664

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]

ACMG classification

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	UniProt
GABBR2	NM_005458.8	c.483T>C	p.Pro161=	synonymous_variant	3/19	ENST00000259455.4
GABBR2	XM_017015331.3	c.189T>C	p.Pro63=	synonymous_variant	2/18

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9963 AN: 152196 Hom.: 559 Cov.: 33

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

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.: 31 AF XY: 0.0329 AC XY: 23903 AN XY: 727170

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.: 33 AF XY: 0.0645 AC XY: 4801 AN XY: 74472

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: 58 AN: 3478

EpiCase AF: 0.0297

EpiControl AF: 0.0295

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Epileptic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

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

Other links and lift over

dbSNP: rs35449008; hg19: chr9-101304302;