rs12618338

Positions:

• chr2-132525481-G-A

Variant summary

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

The NM_001508.3(GPR39):​c.856+107583G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,164 control chromosomes in the GnomAD database, including 3,247 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (3247 hom., cov: 33)
• Consequence: GPR39 NM_001508.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

Genes affected

GPR39 (HGNC:4496): (G protein-coupled receptor 39) This gene is a member of the ghrelin receptor family and encodes a rhodopsin-type G-protein-coupled receptor (GPCR). The encoded protein is involved in zinc-dependent signaling in epithelial tissue in intestines, prostate and salivary glands. The protein may also be involved in the pathophysiology of depression. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR39	NM_001508.3	c.856+107583G>A		intron_variant		ENST00000329321.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR39	ENST00000329321.4	c.856+107583G>A		intron_variant		1	NM_001508.3	P1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28020 AN: 152046 Hom.: 3239 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.184 AC: 28048 AN: 152164 Hom.: 3247 Cov.: 33 AF XY: 0.192 AC XY: 14298 AN XY: 74374

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.196

Alfa AF: 0.173 Hom.: 949

Bravo AF: 0.189

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.74

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: rs12618338; hg19: chr2-133283054;