rs1930139

Positions:

• chr9-98667306-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.321+41111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 151,890 control chromosomes in the GnomAD database, including 38,774 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 0.71 (38774 hom., cov: 30)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.696

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.321+41111G>A		intron_variant		ENST00000259455.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.321+41111G>A		intron_variant		1	NM_005458.8	P1
GABBR2	ENST00000637717.1	c.-64+39938G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107093 AN: 151772 Hom.: 38774 Cov.: 30

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.705 AC: 107121 AN: 151890 Hom.: 38774 Cov.: 30 AF XY: 0.707 AC XY: 52504 AN XY: 74248

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.742

Alfa AF: 0.742 Hom.: 10488

Bravo AF: 0.698

Asia WGS AF: 0.735 AC: 2556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.58

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: rs1930139; hg19: chr9-101429588; COSMIC: COSV52298256;