rs10999212

Positions:

• chr10-70255653-C-A
• chr10-70255653-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_022146.5(NPFFR1):​c.597G>T​(p.Pro199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,593,294 control chromosomes in the GnomAD database, including 55,464 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 0.21 (4289 hom., cov: 32)
  • Exomes 𝑓: 0.26 (51175 hom.)
• Consequence: NPFFR1 NM_022146.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

Genes affected

NPFFR1 (HGNC:17425): (neuropeptide FF receptor 1) Predicted to enable G protein-coupled receptor activity and peptide binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=-1.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPFFR1	NM_022146.5	c.597G>T	p.Pro199=	synonymous_variant	4/4	ENST00000277942.7	NP_071429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPFFR1	ENST00000277942.7	c.597G>T	p.Pro199=	synonymous_variant	4/4	5	NM_022146.5	ENSP00000277942	P1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32356 AN: 151992 Hom.: 4288 Cov.: 32

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.218

GnomAD3 exomes AF: 0.221 AC: 46916 AN: 212232 Hom.: 6052 AF XY: 0.227 AC XY: 26202 AN XY: 115274

Gnomad AFR exome AF: 0.0872

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.00417

Gnomad SAS exome AF: 0.258

Gnomad FIN exome AF: 0.363

Gnomad NFE exome AF: 0.268

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.259 AC: 372834 AN: 1441184 Hom.: 51175 Cov.: 52 AF XY: 0.259 AC XY: 185003 AN XY: 714748

Gnomad4 AFR exome AF: 0.0858

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.00249

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.213 AC: 32357 AN: 152110 Hom.: 4289 Cov.: 32 AF XY: 0.218 AC XY: 16173 AN XY: 74354

Gnomad4 AFR AF: 0.0945

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.216

Alfa AF: 0.238 Hom.: 3004

Bravo AF: 0.190

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	4.9
DANN	Benign	0.91

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: rs10999212; hg19: chr10-72015409; COSMIC: COSV53333147;