rs1930135

Positions:

• chr9-98648850-T-C
• chr9-98648850-T-G

Variant summary

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

The NM_005458.8(GABBR2):​c.321+59567A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,018 control chromosomes in the GnomAD database, including 32,459 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 0.64 (32459 hom., cov: 32)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

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 = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.321+59567A>G		intron_variant		ENST00000259455.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.321+59567A>G		intron_variant		1	NM_005458.8	P1
GABBR2	ENST00000637717.1	c.-64+58394A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97823 AN: 151900 Hom.: 32456 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.644 AC: 97841 AN: 152018 Hom.: 32459 Cov.: 32 AF XY: 0.639 AC XY: 47446 AN XY: 74282

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.671

Alfa AF: 0.721 Hom.: 80793

Bravo AF: 0.628

Asia WGS AF: 0.520 AC: 1807 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.61

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: rs1930135; hg19: chr9-101411132; COSMIC: COSV52297865;