9-98492194-A-C

Position:

• chr9-98492194-A-C

Variant summary

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

The NM_005458.8(GABBR2):​c.732+4219T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,242 control chromosomes in the GnomAD database, including 37,608 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 0.70 (37608 hom., cov: 27)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.732+4219T>G		intron_variant		ENST00000259455.4
GABBR2	XM_005252316.6	c.-43+4219T>G		intron_variant
GABBR2	XM_017015331.3	c.438+4219T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.732+4219T>G		intron_variant		1	NM_005458.8	P1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106130 AN: 151126 Hom.: 37565 Cov.: 27

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.702 AC: 106234 AN: 151242 Hom.: 37608 Cov.: 27 AF XY: 0.706 AC XY: 52150 AN XY: 73820

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.699

Alfa AF: 0.663 Hom.: 42364

Bravo AF: 0.717

Asia WGS AF: 0.841 AC: 2925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.4
DANN	Benign	0.82

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: rs2779552; hg19: chr9-101254476; COSMIC: COSV52297487;