rs4950806

Variant names:

• chr1-201983446-T-C
• rs4950806
• NM_020216.4:c.447+333T>C

Variant summary

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

The NM_001319182.2(RNPEP):​c.-17T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,426,484 control chromosomes in the GnomAD database, including 259,111 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 0.60 (27379 hom., cov: 33)
  • Exomes 𝑓: 0.60 (231732 hom.)
• Consequence: RNPEP NM_001319182.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

Genes affected

RNPEP (HGNC:10078): (arginyl aminopeptidase) Predicted to enable metalloaminopeptidase activity. Predicted to be involved in proteolysis. Located in extracellular exosome. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNPEP	NM_020216.4	c.447+333T>C		intron_variant	Intron 1 of 10	ENST00000295640.9	NP_064601.3
RNPEP	NM_001319182.2	c.-17T>C		5_prime_UTR_variant	Exon 1 of 11		NP_001306111.1
RNPEP	NM_001319183.2	c.-421+333T>C		intron_variant	Intron 1 of 9		NP_001306112.1
RNPEP	NM_001319184.2	c.-275+333T>C		intron_variant	Intron 1 of 9		NP_001306113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNPEP	ENST00000295640.9	c.447+333T>C		intron_variant	Intron 1 of 10	1	NM_020216.4	ENSP00000295640.4

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90975 AN: 151982 Hom.: 27342 Cov.: 33

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.557

GnomAD3 exomes AF: 0.583 AC: 86632 AN: 148574 Hom.: 25449 AF XY: 0.584 AC XY: 46772 AN XY: 80032

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.543

Gnomad ASJ exome AF: 0.572

Gnomad EAS exome AF: 0.511

Gnomad SAS exome AF: 0.594

Gnomad FIN exome AF: 0.613

Gnomad NFE exome AF: 0.600

Gnomad OTH exome AF: 0.573

GnomAD4 exome AF: 0.602 AC: 767307 AN: 1274384 Hom.: 231732 Cov.: 41 AF XY: 0.602 AC XY: 376671 AN XY: 625672

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.538

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.567

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.605

Gnomad4 OTH exome AF: 0.597

GnomAD4 genome AF: 0.599 AC: 91069 AN: 152100 Hom.: 27379 Cov.: 33 AF XY: 0.597 AC XY: 44383 AN XY: 74350

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.553

Alfa AF: 0.597 Hom.: 13021

Bravo AF: 0.591

Asia WGS AF: 0.529 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
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: rs4950806; hg19: chr1-201952574; COSMIC: COSV55239778; COSMIC: COSV55239778;