9-98290276-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005458.8(GABBR2):c.*308A>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 0.00514 in 94,938 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (1 hom., cov: 27)
  • Exomes 𝑓: 0.0035 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABBR2 NM_005458.8 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-98290276-T-G is Benign according to our data. Variant chr9-98290276-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1206699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 489 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.*308A>C		3_prime_UTR_variant	19/19	ENST00000259455.4
GABBR2	XM_005252316.6	c.*308A>C		3_prime_UTR_variant	17/17
GABBR2	XM_017015331.3	c.*308A>C		3_prime_UTR_variant	18/18
GABBR2	XM_017015332.3	c.*308A>C		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.*308A>C		3_prime_UTR_variant	19/19	1	NM_005458.8	P1

Frequencies

GnomAD3 genomes AF: 0.00515 AC: 489 AN: 94920 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00156

Gnomad AMR AF: 0.00192

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00521

Gnomad SAS AF: 0.00335

Gnomad FIN AF: 0.00293

Gnomad MID AF: 0.0168

Gnomad NFE AF: 0.00433

Gnomad OTH AF: 0.00570

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00350 AC: 50 AN: 14286 Hom.: 1 Cov.: 0 AF XY: 0.00363 AC XY: 27 AN XY: 7448

Gnomad4 AFR exome AF: 0.00128

Gnomad4 AMR exome AF: 0.00483

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00293

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0192

Gnomad4 NFE exome AF: 0.00248

Gnomad4 OTH exome AF: 0.00210

GnomAD4 genome AF: 0.00514 AC: 488 AN: 94938 Hom.: 1 Cov.: 27 AF XY: 0.00475 AC XY: 220 AN XY: 46332

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.00201

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00523

Gnomad4 SAS AF: 0.00306

Gnomad4 FIN AF: 0.00293

Gnomad4 NFE AF: 0.00434

Gnomad4 OTH AF: 0.00567

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely 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	-0.81
Cadd	Benign	6.2
Dann	Benign	0.73

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: rs10985754; hg19: chr9-101052558; COSMIC: COSV105008928; COSMIC: COSV105008928;