rs3780428

chr9-98366634-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.1771-3797G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 152,058 control chromosomes in the GnomAD database, including 11,986 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 0.36 (11986 hom., cov: 32)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.1771-3797G>A		intron_variant		ENST00000259455.4
GABBR2	XM_005252316.6	c.997-3797G>A		intron_variant
GABBR2	XM_017015331.3	c.1477-3797G>A		intron_variant
GABBR2	XM_017015332.3	c.997-3797G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.1771-3797G>A		intron_variant		1	NM_005458.8	P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55103 AN: 151940 Hom.: 11963 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.363 AC: 55172 AN: 152058 Hom.: 11986 Cov.: 32 AF XY: 0.355 AC XY: 26366 AN XY: 74328

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.366

Alfa AF: 0.294 Hom.: 14362

Bravo AF: 0.377

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.86
Dann	Benign	0.74

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: rs3780428; hg19: chr9-101128916;