rs10818948

chr9-98454435-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005458.8(GABBR2):c.1000-218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,880 control chromosomes in the GnomAD database, including 7,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7499 hom., cov: 31)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.100

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 9-98454435-C-T is Benign according to our data. Variant chr9-98454435-C-T is described in ClinVar as [Benign]. Clinvar id is 1277138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.1000-218G>A		intron_variant		ENST00000259455.4
GABBR2	XM_005252316.6	c.226-218G>A		intron_variant
GABBR2	XM_017015331.3	c.706-218G>A		intron_variant
GABBR2	XM_017015332.3	c.226-218G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.1000-218G>A		intron_variant		1	NM_005458.8	P1
GABBR2	ENST00000634919.1	n.778-218G>A		intron_variant, non_coding_transcript_variant		5
GABBR2	ENST00000637410.1	n.778-218G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45954 AN: 151762 Hom.: 7491 Cov.: 31

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.303 AC: 45984 AN: 151880 Hom.: 7499 Cov.: 31 AF XY: 0.308 AC XY: 22848 AN XY: 74230

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.292

Alfa AF: 0.324 Hom.: 3151

Bravo AF: 0.298

Asia WGS AF: 0.426 AC: 1480 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.2
Dann	Benign	0.61

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: rs10818948; hg19: chr9-101216717;