9-98290284-T-G

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.*300A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 146,344 control chromosomes in the GnomAD database, including 3,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (3070 hom., cov: 29)
  • Exomes 𝑓: 0.013 (135 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABBR2 NM_005458.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.863

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=-0.83).
• BP6: Variant 9-98290284-T-G is Benign according to our data. Variant chr9-98290284-T-G is described in ClinVar as [Benign]. Clinvar id is 1239107.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.113 AC: 16537 AN: 146292 Hom.: 3069 Cov.: 29

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0509

Gnomad ASJ AF: 0.00580

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00769

Gnomad FIN AF: 0.00133

Gnomad MID AF: 0.0296

Gnomad NFE AF: 0.00780

Gnomad OTH AF: 0.0809

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0127 AC: 441 AN: 34772 Hom.: 135 Cov.: 0 AF XY: 0.0101 AC XY: 179 AN XY: 17792

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.0172

Gnomad4 ASJ exome AF: 0.00233

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00307

Gnomad4 FIN exome AF: 0.000401

Gnomad4 NFE exome AF: 0.00146

Gnomad4 OTH exome AF: 0.0234

GnomAD4 genome AF: 0.113 AC: 16550 AN: 146344 Hom.: 3070 Cov.: 29 AF XY: 0.109 AC XY: 7793 AN XY: 71394

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.0508

Gnomad4 ASJ AF: 0.00580

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00728

Gnomad4 FIN AF: 0.00133

Gnomad4 NFE AF: 0.00780

Gnomad4 OTH AF: 0.0801

Alfa AF: 0.0300 Hom.: 119

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.8
Dann	Benign	0.75

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: rs28634003; hg19: chr9-101052566;