rs2779547

Positions:

• chr9-98480739-T-C

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.798+193A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 151,892 control chromosomes in the GnomAD database, including 45,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.76 (45120 hom., cov: 30)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 9-98480739-T-C is Benign according to our data. Variant chr9-98480739-T-C is described in ClinVar as [Benign]. Clinvar id is 1279836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.798+193A>G		intron_variant		ENST00000259455.4	NP_005449.5
GABBR2	XM_005252316.6	c.24+193A>G		intron_variant			XP_005252373.1
GABBR2	XM_017015331.3	c.504+193A>G		intron_variant			XP_016870820.1
GABBR2	XM_017015332.3	c.24+193A>G		intron_variant			XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.798+193A>G		intron_variant		1	NM_005458.8	ENSP00000259455	P1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116070 AN: 151774 Hom.: 45089 Cov.: 30

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.762

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.765 AC: 116152 AN: 151892 Hom.: 45120 Cov.: 30 AF XY: 0.768 AC XY: 57026 AN XY: 74214

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.817

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.759

Alfa AF: 0.787 Hom.: 6931

Bravo AF: 0.760

Asia WGS AF: 0.835 AC: 2901 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	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.63
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2779547; hg19: chr9-101243021;