9-98290274-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.*310A>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 0.0618 in 120,614 control chromosomes in the GnomAD database, including 325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (325 hom., cov: 30)
  • Exomes 𝑓: 0.0049 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABBR2 NM_005458.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.19

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=-0.82).
• BP6: Variant 9-98290274-T-G is Benign according to our data. Variant chr9-98290274-T-G is described in ClinVar as [Benign]. Clinvar id is 1272136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.*310A>C		3_prime_UTR_variant	19/19	ENST00000259455.4
GABBR2	XM_005252316.6	c.*310A>C		3_prime_UTR_variant	17/17
GABBR2	XM_017015331.3	c.*310A>C		3_prime_UTR_variant	18/18
GABBR2	XM_017015332.3	c.*310A>C		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.*310A>C		3_prime_UTR_variant	19/19	1	NM_005458.8	P1

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 7461 AN: 120602 Hom.: 326 Cov.: 30

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.0430

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.000668

Gnomad SAS AF: 0.0803

Gnomad FIN AF: 0.0430

Gnomad MID AF: 0.107

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.0790

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00494 AC: 74 AN: 14972 Hom.: 5 Cov.: 0 AF XY: 0.00468 AC XY: 36 AN XY: 7698

Gnomad4 AFR exome AF: 0.00419

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0145

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0110

Gnomad4 NFE exome AF: 0.00430

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome AF: 0.0618 AC: 7453 AN: 120614 Hom.: 325 Cov.: 30 AF XY: 0.0598 AC XY: 3509 AN XY: 58722

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.0429

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.000670

Gnomad4 SAS AF: 0.0797

Gnomad4 FIN AF: 0.0430

Gnomad4 NFE AF: 0.0741

Gnomad4 OTH AF: 0.0775

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 21, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.0
Dann	Benign	0.70

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: rs71491759; hg19: chr9-101052556;