rs7250833

Variant names:

• chr19-33446371-C-T
• rs7250833
• NM_000285.4:c.671+16624G>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.671+16624G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,164 control chromosomes in the GnomAD database, including 6,193 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 0.28 (6193 hom., cov: 33)
• Consequence: PEPD NM_000285.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEPD	NM_000285.4	c.671+16624G>A		intron_variant	Intron 9 of 14	ENST00000244137.12	NP_000276.2
PEPD	NM_001166056.2	c.548+31675G>A		intron_variant	Intron 7 of 12		NP_001159528.1
PEPD	NM_001166057.2	c.479+16624G>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.671+16624G>A		intron_variant	Intron 9 of 14	1	NM_000285.4	ENSP00000244137.5

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42210 AN: 152046 Hom.: 6192 Cov.: 33

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.278 AC: 42228 AN: 152164 Hom.: 6193 Cov.: 33 AF XY: 0.270 AC XY: 20052 AN XY: 74386

African (AFR) AF: 0.340 AC: 14124 AN: 41488

American (AMR) AF: 0.232 AC: 3548 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3472

East Asian (EAS) AF: 0.134 AC: 693 AN: 5180

South Asian (SAS) AF: 0.153 AC: 739 AN: 4824

European-Finnish (FIN) AF: 0.170 AC: 1802 AN: 10594

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19452 AN: 67996

Other (OTH) AF: 0.286 AC: 603 AN: 2110

Alfa AF: 0.282 Hom.: 5303

Bravo AF: 0.287

Asia WGS AF: 0.162 AC: 564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.50
DANN	Benign	0.47
PhyloP100		-0.61
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: rs7250833; hg19: chr19-33937277;