rs2241380

Positions:

• chr19-33460220-A-G

Variant summary

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

The NM_000285.4(PEPD):​c.671+2775T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,014 control chromosomes in the GnomAD database, including 13,991 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 0.42 (13991 hom., cov: 32)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

Genes affected

PEPD (HGNC:8840): (peptidase D) This gene encodes a member of the peptidase family. The protein forms a homodimer that hydrolyzes dipeptides or tripeptides with C-terminal proline or hydroxyproline residues. The enzyme serves an important role in the recycling of proline, and may be rate limiting for the production of collagen. Mutations in this gene result in prolidase deficiency, which is characterized by the excretion of large amount of di- and tri-peptides containing proline. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEPD	NM_000285.4	c.671+2775T>C		intron_variant		ENST00000244137.12	NP_000276.2
PEPD	NM_001166056.2	c.548+17826T>C		intron_variant			NP_001159528.1
PEPD	NM_001166057.2	c.479+2775T>C		intron_variant			NP_001159529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEPD	ENST00000244137.12	c.671+2775T>C		intron_variant		1	NM_000285.4	ENSP00000244137	P1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63324 AN: 151896 Hom.: 13975 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.417 AC: 63392 AN: 152014 Hom.: 13991 Cov.: 32 AF XY: 0.414 AC XY: 30733 AN XY: 74298

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.402

Alfa AF: 0.392 Hom.: 1510

Bravo AF: 0.434

Asia WGS AF: 0.290 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.11
DANN	Benign	0.29

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: rs2241380; hg19: chr19-33951126;