rs944688

Positions:

• chr9-98601678-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.322-23606G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,052 control chromosomes in the GnomAD database, including 9,271 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 0.34 (9271 hom., cov: 32)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.322-23606G>A		intron_variant		ENST00000259455.4	NP_005449.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.322-23606G>A		intron_variant		1	NM_005458.8	ENSP00000259455	P1
GABBR2	ENST00000637717.1	c.-63-23606G>A		intron_variant		5		ENSP00000490789
GABBR2	ENST00000634227.1	n.95+5878G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51651 AN: 151934 Hom.: 9265 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.340 AC: 51697 AN: 152052 Hom.: 9271 Cov.: 32 AF XY: 0.334 AC XY: 24801 AN XY: 74322

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.302

Alfa AF: 0.327 Hom.: 1789

Bravo AF: 0.343

Asia WGS AF: 0.223 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs944688; hg19: chr9-101363960;