chr9-98380522-C-T

Position:

• chr9-98380522-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005458.8(GABBR2):​c.1662+5118G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,160 control chromosomes in the GnomAD database, including 11,840 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency: Genomes: 𝑓 0.37 (11840 hom., cov: 34)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABBR2	NM_005458.8	c.1662+5118G>A		intron_variant		ENST00000259455.4
GABBR2	XM_005252316.6	c.888+5118G>A		intron_variant
GABBR2	XM_017015331.3	c.1368+5118G>A		intron_variant
GABBR2	XM_017015332.3	c.888+5118G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4	c.1662+5118G>A		intron_variant		1	NM_005458.8	P1
GABBR2	ENST00000634314.1	n.167+5118G>A		intron_variant, non_coding_transcript_variant		3
GABBR2	ENST00000637410.1	n.1440+5118G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56882 AN: 152042 Hom.: 11834 Cov.: 34

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.386

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.374 AC: 56885 AN: 152160 Hom.: 11840 Cov.: 34 AF XY: 0.376 AC XY: 27942 AN XY: 74368

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.384

Alfa AF: 0.407 Hom.: 4026

Bravo AF: 0.355

Asia WGS AF: 0.387 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.48

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: rs3780422; hg19: chr9-101142804;