rs11084731

Variant names:

• chr19-33423259-A-T
• rs11084731
• NM_000285.4:c.672-9616T>A

Variant summary

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

The NM_000285.4(PEPD):​c.672-9616T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,094 control chromosomes in the GnomAD database, including 10,961 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 (10961 hom., cov: 33)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375
• Publications: 2 publications found

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]

PEPD Gene-Disease associations (from GenCC):

• prolidase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEPD	NM_000285.4	c.672-9616T>A		intron_variant	Intron 9 of 14	ENST00000244137.12	NP_000276.2
PEPD	NM_001166056.2	c.549-9616T>A		intron_variant	Intron 7 of 12		NP_001159528.1
PEPD	NM_001166057.2	c.480-9616T>A		intron_variant	Intron 7 of 12		NP_001159529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEPD	ENST00000244137.12	c.672-9616T>A		intron_variant	Intron 9 of 14	1	NM_000285.4	ENSP00000244137.5

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55929 AN: 151976 Hom.: 10942 Cov.: 33

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.368 AC: 55994 AN: 152094 Hom.: 10961 Cov.: 33 AF XY: 0.367 AC XY: 27295 AN XY: 74374

African (AFR) AF: 0.505 AC: 20946 AN: 41474

American (AMR) AF: 0.353 AC: 5396 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 844 AN: 3468

East Asian (EAS) AF: 0.320 AC: 1653 AN: 5170

South Asian (SAS) AF: 0.245 AC: 1182 AN: 4818

European-Finnish (FIN) AF: 0.359 AC: 3800 AN: 10586

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21089 AN: 67978

Other (OTH) AF: 0.330 AC: 696 AN: 2108

Alfa AF: 0.348 Hom.: 1185

Bravo AF: 0.379

Asia WGS AF: 0.291 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.73
PhyloP100		0.38
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: rs11084731; hg19: chr19-33914165;