rs4239576

Positions:

• chr19-33424454-A-G
• chr19-33424454-A-T

Variant summary

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

The NM_000285.4(PEPD):​c.672-10811T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,114 control chromosomes in the GnomAD database, including 11,378 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 0.37 (11378 hom., cov: 33)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEPD	NM_000285.4	c.672-10811T>C		intron_variant		ENST00000244137.12
PEPD	NM_001166056.2	c.549-10811T>C		intron_variant
PEPD	NM_001166057.2	c.480-10811T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEPD	ENST00000244137.12	c.672-10811T>C		intron_variant		1	NM_000285.4	P1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56708 AN: 151996 Hom.: 11357 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.373 AC: 56777 AN: 152114 Hom.: 11378 Cov.: 33 AF XY: 0.372 AC XY: 27650 AN XY: 74370

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.335

Alfa AF: 0.313 Hom.: 10172

Bravo AF: 0.385

Asia WGS AF: 0.303 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.0
DANN	Benign	0.69

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: rs4239576; hg19: chr19-33915360;