11-94398973-A-G

Position:

• chr11-94398973-A-G

Variant summary

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

The NM_016540.4(GPR83):​c.387+1888T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,120 control chromosomes in the GnomAD database, including 4,556 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 0.23 (4556 hom., cov: 32)
• Consequence: GPR83 NM_016540.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559

Genes affected

GPR83 (HGNC:4523): (G protein-coupled receptor 83) Predicted to enable neuropeptide receptor activity. Predicted to be involved in neuropeptide signaling pathway. Predicted to act upstream of or within response to glucocorticoid. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR83	NM_016540.4	c.387+1888T>C		intron_variant		ENST00000243673.7	NP_057624.3
GPR83	NM_001330345.2	c.387+1888T>C		intron_variant			NP_001317274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR83	ENST00000243673.7	c.387+1888T>C		intron_variant		1	NM_016540.4	ENSP00000243673.2
GPR83	ENST00000539203.2	c.387+1888T>C		intron_variant		5		ENSP00000441550.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34891 AN: 152002 Hom.: 4558 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.229 AC: 34908 AN: 152120 Hom.: 4556 Cov.: 32 AF XY: 0.229 AC XY: 17005 AN XY: 74362

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.220

Alfa AF: 0.272 Hom.: 5094

Bravo AF: 0.224

Asia WGS AF: 0.226 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.57

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: rs3758785; hg19: chr11-94132139; COSMIC: COSV54720968;