rs2491397

chr9-98442880-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.1236+11101G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,104 control chromosomes in the GnomAD database, including 19,374 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 0.49 (19374 hom., cov: 32)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.1236+11101G>A		intron_variant		ENST00000259455.4
GABBR2	XM_005252316.6	c.462+11101G>A		intron_variant
GABBR2	XM_017015331.3	c.942+11101G>A		intron_variant
GABBR2	XM_017015332.3	c.462+11101G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.1236+11101G>A		intron_variant		1	NM_005458.8	P1
GABBR2	ENST00000637410.1	n.1014+11101G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75239 AN: 151986 Hom.: 19378 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.495 AC: 75255 AN: 152104 Hom.: 19374 Cov.: 32 AF XY: 0.488 AC XY: 36293 AN XY: 74332

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.512

Alfa AF: 0.547 Hom.: 29653

Bravo AF: 0.485

Asia WGS AF: 0.299 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	8.1
Dann	Benign	0.60

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: rs2491397; hg19: chr9-101205162;