NM_016540.4:c.387+1888T>C

Variant names:

• chr11-94398973-A-G
• rs3758785
• NM_016540.4:c.387+1888T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016540.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR83	NM_016540.4	MANE Select	c.387+1888T>C		intron	N/A	NP_057624.3
	GPR83	NM_001330345.2		c.387+1888T>C		intron	N/A	NP_001317274.1	Q9NYM4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR83	ENST00000243673.7	TSL:1 MANE Select	c.387+1888T>C		intron	N/A	ENSP00000243673.2	Q9NYM4-1
	GPR83	ENST00000539203.2	TSL:5	c.387+1888T>C		intron	N/A	ENSP00000441550.1	Q9NYM4-2

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

African (AFR) AF: 0.106 AC: 4392 AN: 41518

American (AMR) AF: 0.266 AC: 4058 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 845 AN: 3472

East Asian (EAS) AF: 0.260 AC: 1344 AN: 5172

South Asian (SAS) AF: 0.230 AC: 1107 AN: 4818

European-Finnish (FIN) AF: 0.281 AC: 2968 AN: 10576

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19341 AN: 67970

Other (OTH) AF: 0.220 AC: 463 AN: 2108

Alfa AF: 0.271 Hom.: 16356

Bravo AF: 0.224

Asia WGS AF: 0.226 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.57
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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