9-98542066-C-T

Position:

• chr9-98542066-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005458.8(GABBR2):​c.460-23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,604,824 control chromosomes in the GnomAD database, including 43,661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3676 hom., cov: 33)
  • Exomes 𝑓: 0.22 (39985 hom.)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.87

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-98542066-C-T is Benign according to our data. Variant chr9-98542066-C-T is described in ClinVar as [Benign]. Clinvar id is 1277285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.460-23G>A		intron_variant		ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3	c.166-23G>A		intron_variant			XP_016870820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.460-23G>A		intron_variant		1	NM_005458.8	ENSP00000259455.2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29776 AN: 152056 Hom.: 3666 Cov.: 33

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.215

GnomAD3 exomes AF: 0.248 AC: 61014 AN: 246172 Hom.: 8609 AF XY: 0.246 AC XY: 32716 AN XY: 133118

Gnomad AFR exome AF: 0.0623

Gnomad AMR exome AF: 0.312

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.498

Gnomad SAS exome AF: 0.226

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.218

Gnomad OTH exome AF: 0.242

GnomAD4 exome AF: 0.224 AC: 326005 AN: 1452650 Hom.: 39985 Cov.: 29 AF XY: 0.225 AC XY: 162322 AN XY: 722848

Gnomad4 AFR exome AF: 0.0543

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.546

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.196 AC: 29795 AN: 152174 Hom.: 3676 Cov.: 33 AF XY: 0.205 AC XY: 15222 AN XY: 74390

Gnomad4 AFR AF: 0.0663

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.218

Alfa AF: 0.215 Hom.: 3811

Bravo AF: 0.193

Asia WGS AF: 0.331 AC: 1152 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.84
CADD	Benign	1.8
DANN	Benign	0.64

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: rs2184026; hg19: chr9-101304348; COSMIC: COSV52304571;