9-98290576-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_005458.8(GABBR2):c.*8A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,368,814 control chromosomes in the GnomAD database, including 10,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (3470 hom., cov: 31)
  • Exomes 𝑓: 0.097 (7461 hom.)
• Consequence: GABBR2 NM_005458.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.64

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=-0.37).
• BP6: Variant 9-98290576-T-C is Benign according to our data. Variant chr9-98290576-T-C is described in ClinVar as [Benign]. Clinvar id is 1278627.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25849 AN: 151852 Hom.: 3463 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.0430

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0618

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.106 AC: 9386 AN: 88824 Hom.: 765 AF XY: 0.0977 AC XY: 4645 AN XY: 47538

Gnomad AFR exome AF: 0.376

Gnomad AMR exome AF: 0.0803

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.213

Gnomad SAS exome AF: 0.0222

Gnomad FIN exome AF: 0.0551

Gnomad NFE exome AF: 0.0851

Gnomad OTH exome AF: 0.0895

GnomAD4 exome AF: 0.0965 AC: 117461 AN: 1216844 Hom.: 7461 Cov.: 31 AF XY: 0.0940 AC XY: 55127 AN XY: 586412

Gnomad4 AFR exome AF: 0.377

Gnomad4 AMR exome AF: 0.0964

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.284

Gnomad4 SAS exome AF: 0.0251

Gnomad4 FIN exome AF: 0.0591

Gnomad4 NFE exome AF: 0.0875

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.170 AC: 25884 AN: 151970 Hom.: 3470 Cov.: 31 AF XY: 0.166 AC XY: 12301 AN XY: 74300

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0997

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.0298

Gnomad4 FIN AF: 0.0618

Gnomad4 NFE AF: 0.0895

Gnomad4 OTH AF: 0.153

Alfa AF: 0.158 Hom.: 719

Bravo AF: 0.187

Asia WGS AF: 0.155 AC: 540 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	15
Dann	Benign	0.79

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: rs2304391; hg19: chr9-101052858;