9-98630473-C-T

Position:

• chr9-98630473-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005458.8(GABBR2):​c.322-52401G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 152,056 control chromosomes in the GnomAD database, including 36,632 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36632 hom., cov: 31)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.322-52401G>A		intron_variant		ENST00000259455.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.322-52401G>A		intron_variant		1	NM_005458.8	P1
GABBR2	ENST00000637717.1	c.-63-52401G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104391 AN: 151940 Hom.: 36627 Cov.: 31

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.687 AC: 104423 AN: 152056 Hom.: 36632 Cov.: 31 AF XY: 0.682 AC XY: 50690 AN XY: 74310

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.837

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.700

Alfa AF: 0.756 Hom.: 33419

Bravo AF: 0.669

Asia WGS AF: 0.562 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.56

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: rs1547272; hg19: chr9-101392755;