9-98290280-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.*303_*304insC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 174,850 control chromosomes in the GnomAD database, including 2,830 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (2738 hom., cov: 29)
  • Exomes 𝑓: 0.011 (92 hom.)
• Consequence: GABBR2 NM_005458.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.197

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 9-98290280-T-TG is Benign according to our data. Variant chr9-98290280-T-TG is described in ClinVar as [Benign]. Clinvar id is 1296636.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.*303_*304insC		3_prime_UTR_variant	19/19	ENST00000259455.4
GABBR2	XM_005252316.6	c.*303_*304insC		3_prime_UTR_variant	17/17
GABBR2	XM_017015331.3	c.*303_*304insC		3_prime_UTR_variant	18/18
GABBR2	XM_017015332.3	c.*303_*304insC		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.*303_*304insC		3_prime_UTR_variant	19/19	1	NM_005458.8	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15043 AN: 144558 Hom.: 2738 Cov.: 29

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00548

Gnomad SAS AF: 0.00129

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0195

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.0711

GnomAD4 exome AF: 0.0107 AC: 324 AN: 30242 Hom.: 92 Cov.: 0 AF XY: 0.00907 AC XY: 140 AN XY: 15434

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.00801

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000460

Gnomad4 OTH exome AF: 0.0157

GnomAD4 genome AF: 0.104 AC: 15057 AN: 144608 Hom.: 2738 Cov.: 29 AF XY: 0.101 AC XY: 7089 AN XY: 70536

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.0350

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00550

Gnomad4 SAS AF: 0.00129

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00112

Gnomad4 OTH AF: 0.0704

Alfa AF: 0.0772 Hom.: 4

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 06, 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: rs550710050; hg19: chr9-101052562;