rs2900512

chr9-98555639-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005458.8(GABBR2):c.460-13596G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,028 control chromosomes in the GnomAD database, including 3,729 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 0.21 (3727 hom., cov: 32)
  • Exomes 𝑓: 0.31 (2 hom.)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.665

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.460-13596G>A		intron_variant		ENST00000259455.4
GABBR2	XM_017015331.3	c.165+14G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.460-13596G>A		intron_variant		1	NM_005458.8	P1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32406 AN: 151878 Hom.: 3722 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.313 AC: 10 AN: 32 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 7 AN XY: 28

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.286

GnomAD4 genome AF: 0.213 AC: 32441 AN: 151996 Hom.: 3727 Cov.: 32 AF XY: 0.211 AC XY: 15656 AN XY: 74278

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.174

Alfa AF: 0.192 Hom.: 4630

Bravo AF: 0.212

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	16
Dann	Benign	0.77

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: rs2900512; hg19: chr9-101317921;