9-98290279-T-G

Position:

• chr9-98290279-T-G

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.*305A>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 0.0565 in 132,534 control chromosomes in the GnomAD database, including 327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (327 hom., cov: 31)
  • Exomes 𝑓: 0.0048 (13 hom.)
  • Failed GnomAD Quality Control
• Consequence: GABBR2 NM_005458.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.197

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=-0.8).
• BP6: Variant 9-98290279-T-G is Benign according to our data. Variant chr9-98290279-T-G is described in ClinVar as [Benign]. Clinvar id is 1178247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.*305A>C		3_prime_UTR_variant	19/19	ENST00000259455.4	NP_005449.5
GABBR2	XM_005252316.6	c.*305A>C		3_prime_UTR_variant	17/17		XP_005252373.1
GABBR2	XM_017015331.3	c.*305A>C		3_prime_UTR_variant	18/18		XP_016870820.1
GABBR2	XM_017015332.3	c.*305A>C		3_prime_UTR_variant	16/16		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.*305A>C		3_prime_UTR_variant	19/19	1	NM_005458.8	ENSP00000259455	P1

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 7497 AN: 132500 Hom.: 328 Cov.: 31

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.000982

Gnomad SAS AF: 0.0789

Gnomad FIN AF: 0.0402

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.0721

Gnomad OTH AF: 0.0734

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00483 AC: 120 AN: 24866 Hom.: 13 Cov.: 0 AF XY: 0.00465 AC XY: 59 AN XY: 12676

Gnomad4 AFR exome AF: 0.00636

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0206

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00895

Gnomad4 NFE exome AF: 0.00433

Gnomad4 OTH exome AF: 0.00729

GnomAD4 genome AF: 0.0565 AC: 7489 AN: 132534 Hom.: 327 Cov.: 31 AF XY: 0.0546 AC XY: 3525 AN XY: 64518

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.0402

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.000985

Gnomad4 SAS AF: 0.0784

Gnomad4 FIN AF: 0.0402

Gnomad4 NFE AF: 0.0721

Gnomad4 OTH AF: 0.0717

Alfa AF: 0.0151 Hom.: 10

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	Aug 21, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.76

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: rs77626796; hg19: chr9-101052561;