rs4950806

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020216.4(RNPEP):​c.447+333T>C variant causes a intron 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_020216.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020216.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNPEP	NM_020216.4	MANE Select	c.447+333T>C		intron	N/A	NP_064601.3
	RNPEP	NM_001319182.2		c.-17T>C		5_prime_UTR	Exon 1 of 11	NP_001306111.1
	RNPEP	NM_001319183.2		c.-421+333T>C		intron	N/A	NP_001306112.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNPEP	ENST00000295640.9	TSL:1 MANE Select	c.447+333T>C		intron	N/A	ENSP00000295640.4
	RNPEP	ENST00000471105.5	TSL:1	n.159+333T>C		intron	N/A
	RNPEP	ENST00000478617.5	TSL:5	n.72T>C		non_coding_transcript_exon	Exon 1 of 8

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

GnomAD2 exomes AF: 0.583 AC: 86632 AN: 148574 AF XY: 0.584

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 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

African (AFR) AF: 0.625 AC: 18009 AN: 28836

American (AMR) AF: 0.538 AC: 16995 AN: 31602

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 12127 AN: 21154

East Asian (EAS) AF: 0.567 AC: 13846 AN: 24418

South Asian (SAS) AF: 0.603 AC: 46548 AN: 77204

European-Finnish (FIN) AF: 0.617 AC: 22325 AN: 36178

Middle Eastern (MID) AF: 0.505 AC: 2555 AN: 5056

European-Non Finnish (NFE) AF: 0.605 AC: 604805 AN: 999556

Other (OTH) AF: 0.597 AC: 30097 AN: 50380

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

African (AFR) AF: 0.620 AC: 25731 AN: 41486

American (AMR) AF: 0.531 AC: 8114 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 2000 AN: 3470

East Asian (EAS) AF: 0.534 AC: 2760 AN: 5166

South Asian (SAS) AF: 0.594 AC: 2870 AN: 4832

European-Finnish (FIN) AF: 0.609 AC: 6434 AN: 10564

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41157 AN: 67986

Other (OTH) AF: 0.553 AC: 1170 AN: 2114

Alfa AF: 0.599 Hom.: 67105

Bravo AF: 0.591

Asia WGS AF: 0.529 AC: 1840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.4
DANN	Benign	0.57
PhyloP100		-0.048
PromoterAI		-0.015	Neutral
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: rs4950806; hg19: chr1-201952574; COSMIC: COSV55239778; COSMIC: COSV55239778;