9-98515399-T-C

Position:

• chr9-98515399-T-C

Variant summary

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

The NM_005458.8(GABBR2):​c.631-18885A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,980 control chromosomes in the GnomAD database, including 18,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: 𝑓 0.49 (18512 hom., cov: 32)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.631-18885A>G		intron_variant		ENST00000259455.4	NP_005449.5
GABBR2	XM_005252316.6	c.-144-18885A>G		intron_variant			XP_005252373.1
GABBR2	XM_017015331.3	c.337-18885A>G		intron_variant			XP_016870820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.631-18885A>G		intron_variant		1	NM_005458.8	ENSP00000259455	P1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73796 AN: 151862 Hom.: 18491 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.486 AC: 73868 AN: 151980 Hom.: 18512 Cov.: 32 AF XY: 0.493 AC XY: 36606 AN XY: 74244

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.513

Alfa AF: 0.502 Hom.: 32962

Bravo AF: 0.488

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.8
DANN	Benign	0.33

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: rs2779562; hg19: chr9-101277681;