9-98341309-G-A

Position:

• chr9-98341309-G-A

Variant summary

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

The ENST00000259455.4(GABBR2):​c.1893+21406C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,114 control chromosomes in the GnomAD database, including 7,021 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 0.30 (7021 hom., cov: 33)
• Consequence: GABBR2 ENST00000259455.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.1893+21406C>T		intron_variant		ENST00000259455.4	NP_005449.5
GABBR2	XM_005252316.6	c.1119+21406C>T		intron_variant			XP_005252373.1
GABBR2	XM_017015331.3	c.1599+21406C>T		intron_variant			XP_016870820.1
GABBR2	XM_017015332.3	c.1119+21406C>T		intron_variant			XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.1893+21406C>T		intron_variant		1	NM_005458.8	ENSP00000259455	P1
GABBR2	ENST00000634457.1	c.231+21406C>T		intron_variant		5		ENSP00000489352
GABBR2	ENST00000635462.1	n.388+21406C>T		intron_variant, non_coding_transcript_variant		2
GABBR2	ENST00000637410.1	n.1671+21406C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45563 AN: 151996 Hom.: 7031 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.300 AC: 45568 AN: 152114 Hom.: 7021 Cov.: 33 AF XY: 0.301 AC XY: 22384 AN XY: 74348

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.288

Alfa AF: 0.290 Hom.: 4513

Bravo AF: 0.299

Asia WGS AF: 0.350 AC: 1217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.63

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: rs1435252; hg19: chr9-101103591;