9-98290284-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005458.8(GABBR2):c.*299_*300insC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 146,310 control chromosomes in the GnomAD database, including 521 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.058 (521 hom., cov: 29)
  • Exomes 𝑓: 0.0018 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABBR2 NM_005458.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.470

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 -10 ACMG points.

• BP6: Variant 9-98290284-T-TG is Benign according to our data. Variant chr9-98290284-T-TG is described in ClinVar as [Benign]. Clinvar id is 1263758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.*299_*300insC		3_prime_UTR_variant	19/19	ENST00000259455.4
GABBR2	XM_005252316.6	c.*299_*300insC		3_prime_UTR_variant	17/17
GABBR2	XM_017015331.3	c.*299_*300insC		3_prime_UTR_variant	18/18
GABBR2	XM_017015332.3	c.*299_*300insC		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.*299_*300insC		3_prime_UTR_variant	19/19	1	NM_005458.8	P1

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8438 AN: 146258 Hom.: 518 Cov.: 29

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00881

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.00870

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00491

Gnomad FIN AF: 0.00472

Gnomad MID AF: 0.0395

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0427

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00181 AC: 63 AN: 34756 Hom.: 2 Cov.: 0 AF XY: 0.00186 AC XY: 33 AN XY: 17784

Gnomad4 AFR exome AF: 0.0572

Gnomad4 AMR exome AF: 0.00304

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000803

Gnomad4 NFE exome AF: 0.000442

Gnomad4 OTH exome AF: 0.00260

GnomAD4 genome AF: 0.0578 AC: 8457 AN: 146310 Hom.: 521 Cov.: 29 AF XY: 0.0551 AC XY: 3932 AN XY: 71390

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0313

Gnomad4 ASJ AF: 0.00870

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00492

Gnomad4 FIN AF: 0.00472

Gnomad4 NFE AF: 0.0232

Gnomad4 OTH AF: 0.0422

Alfa AF: 0.0428 Hom.: 2

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

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs1297371720; hg19: chr9-101052566;