9-98453895-T-C

Position:

• chr9-98453895-T-C

Variant summary

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

The ENST00000259455.4(GABBR2):​c.1236+86A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 892,898 control chromosomes in the GnomAD database, including 1,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (194 hom., cov: 32)
  • Exomes 𝑓: 0.056 (1451 hom.)
• Consequence: GABBR2 ENST00000259455.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.53

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 9-98453895-T-C is Benign according to our data. Variant chr9-98453895-T-C is described in ClinVar as [Benign]. Clinvar id is 1264838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.1236+86A>G		intron_variant		ENST00000259455.4	NP_005449.5
GABBR2	XM_005252316.6	c.462+86A>G		intron_variant			XP_005252373.1
GABBR2	XM_017015331.3	c.942+86A>G		intron_variant			XP_016870820.1
GABBR2	XM_017015332.3	c.462+86A>G		intron_variant			XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.1236+86A>G		intron_variant		1	NM_005458.8	ENSP00000259455	P1
GABBR2	ENST00000637410.1	n.1014+86A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6413 AN: 152136 Hom.: 195 Cov.: 32

Gnomad AFR AF: 0.00997

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0529

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.0406

GnomAD4 exome AF: 0.0558 AC: 41336 AN: 740644 Hom.: 1451 AF XY: 0.0548 AC XY: 21423 AN XY: 390628

Gnomad4 AFR exome AF: 0.0102

Gnomad4 AMR exome AF: 0.0738

Gnomad4 ASJ exome AF: 0.0236

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.0475

Gnomad4 FIN exome AF: 0.0598

Gnomad4 NFE exome AF: 0.0514

Gnomad4 OTH exome AF: 0.0505

GnomAD4 genome AF: 0.0421 AC: 6414 AN: 152254 Hom.: 194 Cov.: 32 AF XY: 0.0435 AC XY: 3235 AN XY: 74436

Gnomad4 AFR AF: 0.00992

Gnomad4 AMR AF: 0.0498

Gnomad4 ASJ AF: 0.0208

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.0586

Gnomad4 NFE AF: 0.0503

Gnomad4 OTH AF: 0.0406

Alfa AF: 0.0514 Hom.: 156

Bravo AF: 0.0415

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.51

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: rs3802477; hg19: chr9-101216177; COSMIC: COSV52303061; COSMIC: COSV52303061;