rs4743221

Positions:

• chr9-98416347-C-A
• chr9-98416347-C-G
• chr9-98416347-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.1237-10206G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,132 control chromosomes in the GnomAD database, including 46,013 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 0.78 (46013 hom., cov: 33)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.1237-10206G>T		intron_variant		ENST00000259455.4	NP_005449.5
GABBR2	XM_005252316.6	c.463-10206G>T		intron_variant			XP_005252373.1
GABBR2	XM_017015331.3	c.943-10206G>T		intron_variant			XP_016870820.1
GABBR2	XM_017015332.3	c.463-10206G>T		intron_variant			XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.1237-10206G>T		intron_variant		1	NM_005458.8	ENSP00000259455	P1
GABBR2	ENST00000637410.1	n.1015-10206G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118062 AN: 152014 Hom.: 45970 Cov.: 33

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.777 AC: 118154 AN: 152132 Hom.: 46013 Cov.: 33 AF XY: 0.778 AC XY: 57891 AN XY: 74366

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.793

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.806

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.763

Alfa AF: 0.788 Hom.: 43883

Bravo AF: 0.774

Asia WGS AF: 0.801 AC: 2784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
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: rs4743221; hg19: chr9-101178629;