chr9-98322519-G-C

Position:

• chr9-98322519-G-C

Variant summary

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

The ENST00000259455.4(GABBR2):​c.1894-11314C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,472 control chromosomes in the GnomAD database, including 3,511 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 0.19 (3511 hom., cov: 29)
• Consequence: GABBR2 ENST00000259455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.718

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.1894-11314C>G		intron_variant		ENST00000259455.4	NP_005449.5
GABBR2	XM_005252316.6	c.1120-11314C>G		intron_variant			XP_005252373.1
GABBR2	XM_017015331.3	c.1600-11314C>G		intron_variant			XP_016870820.1
GABBR2	XM_017015332.3	c.1120-11314C>G		intron_variant			XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.1894-11314C>G		intron_variant		1	NM_005458.8	ENSP00000259455	P1
GABBR2	ENST00000634457.1	c.232-16174C>G		intron_variant		5		ENSP00000489352
GABBR2	ENST00000635462.1	n.389-11314C>G		intron_variant, non_coding_transcript_variant		2
GABBR2	ENST00000637410.1	n.1672-11314C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29136 AN: 151354 Hom.: 3512 Cov.: 29

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.192 AC: 29136 AN: 151472 Hom.: 3511 Cov.: 29 AF XY: 0.196 AC XY: 14522 AN XY: 73952

Gnomad4 AFR AF: 0.0478

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.214

Alfa AF: 0.222 Hom.: 539

Bravo AF: 0.182

Asia WGS AF: 0.256 AC: 892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.50

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: rs998952; hg19: chr9-101084801;