9-98481082-T-G

Variant names:

• chr9-98481082-T-G
• rs2808557
• NM_005458.8:c.733-85A>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005458.8(GABBR2):​c.733-85A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 864,568 control chromosomes in the GnomAD database, including 282,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43591 hom., cov: 32)
  • Exomes 𝑓: 0.82 (239035 hom.)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0470

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-98481082-T-G is Benign according to our data. Variant chr9-98481082-T-G is described in ClinVar as [Benign]. Clinvar id is 1223286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.733-85A>C		intron_variant	Intron 4 of 18	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3	c.439-85A>C		intron_variant	Intron 3 of 17		XP_016870820.1
GABBR2	XM_005252316.6	c.-42-85A>C		intron_variant	Intron 2 of 16		XP_005252373.1
GABBR2	XM_017015332.3	c.-42-85A>C		intron_variant	Intron 1 of 15		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.733-85A>C		intron_variant	Intron 4 of 18	1	NM_005458.8	ENSP00000259455.2

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113539 AN: 151994 Hom.: 43559 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.750

GnomAD4 exome AF: 0.817 AC: 582078 AN: 712456 Hom.: 239035 AF XY: 0.818 AC XY: 312756 AN XY: 382350

Gnomad4 AFR exome AF: 0.546

Gnomad4 AMR exome AF: 0.866

Gnomad4 ASJ exome AF: 0.807

Gnomad4 EAS exome AF: 0.909

Gnomad4 SAS exome AF: 0.822

Gnomad4 FIN exome AF: 0.824

Gnomad4 NFE exome AF: 0.818

Gnomad4 OTH exome AF: 0.796

GnomAD4 genome AF: 0.747 AC: 113620 AN: 152112 Hom.: 43591 Cov.: 32 AF XY: 0.751 AC XY: 55850 AN XY: 74372

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.747

Alfa AF: 0.783 Hom.: 10417

Bravo AF: 0.739

Asia WGS AF: 0.829 AC: 2880 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.55

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: rs2808557; hg19: chr9-101243364;