9-98290275-T-TC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_005458.8(GABBR2):c.*308_*309insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0056 in 138,558 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (5 hom., cov: 27)
  • Exomes 𝑓: 0.0013 (3 hom.)
• 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.

• BP6: Variant 9-98290275-T-TC is Benign according to our data. Variant chr9-98290275-T-TC is described in ClinVar as [Likely_benign]. Clinvar id is 1193790.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00617 (754/122162) while in subpopulation AFR AF= 0.0363 (713/19626). AF 95% confidence interval is 0.0341. There are 5 homozygotes in gnomad4. There are 364 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd at 753 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.*308_*309insG		3_prime_UTR_variant	19/19	ENST00000259455.4
GABBR2	XM_005252316.6	c.*308_*309insG		3_prime_UTR_variant	17/17
GABBR2	XM_017015331.3	c.*308_*309insG		3_prime_UTR_variant	18/18
GABBR2	XM_017015332.3	c.*308_*309insG		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.*308_*309insG		3_prime_UTR_variant	19/19	1	NM_005458.8	P1

Frequencies

GnomAD3 genomes AF: 0.00616 AC: 753 AN: 122148 Hom.: 5 Cov.: 27

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00178

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000227

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00340

Gnomad NFE AF: 0.000124

Gnomad OTH AF: 0.00392

GnomAD4 exome AF: 0.00134 AC: 22 AN: 16396 Hom.: 3 Cov.: 0 AF XY: 0.00130 AC XY: 11 AN XY: 8442

Gnomad4 AFR exome AF: 0.0220

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000973

Gnomad4 OTH exome AF: 0.00368

GnomAD4 genome AF: 0.00617 AC: 754 AN: 122162 Hom.: 5 Cov.: 27 AF XY: 0.00610 AC XY: 364 AN XY: 59640

Gnomad4 AFR AF: 0.0363

Gnomad4 AMR AF: 0.00178

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000227

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000124

Gnomad4 OTH AF: 0.00390

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

Sep 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs796154585; hg19: chr9-101052557;