19-18357076-T-C

Variant names:

• chr19-18357076-T-C
• rs7248363
• NM_017712.4:c.205-307T>C

Variant summary

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

The NM_017712.4(PGPEP1):​c.205-307T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 152,216 control chromosomes in the GnomAD database, including 41,965 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 0.74 (41965 hom., cov: 34)
• Consequence: PGPEP1 NM_017712.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 16 publications found

Genes affected

PGPEP1 (HGNC:13568): (pyroglutamyl-peptidase I) The gene encodes a cysteine protease and member of the peptidase C15 family of proteins. The encoded protein cleaves amino terminal pyroglutamate residues from protein substrates including thyrotropin-releasing hormone and other neuropeptides. Expression of this gene may be downregulated in colorectal cancer, while activity of the encoded protein may be negatively correlated with cancer progression in colorectal cancer patients. Activity of the encoded protease may also be altered in other disease states including in liver cirrhosis, which is associated with reduced protease activity, and in necrozoospermia, which is associated with elevated protease activity. [provided by RefSeq, Jul 2016]

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 (SAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGPEP1	NM_017712.4	c.205-307T>C		intron_variant	Intron 3 of 4	ENST00000269919.11	NP_060182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGPEP1	ENST00000269919.11	c.205-307T>C		intron_variant	Intron 3 of 4	1	NM_017712.4	ENSP00000269919.3

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112476 AN: 152098 Hom.: 41935 Cov.: 34

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.739 AC: 112555 AN: 152216 Hom.: 41965 Cov.: 34 AF XY: 0.740 AC XY: 55041 AN XY: 74424

African (AFR) AF: 0.661 AC: 27466 AN: 41538

American (AMR) AF: 0.801 AC: 12236 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2840 AN: 3472

East Asian (EAS) AF: 0.600 AC: 3102 AN: 5168

South Asian (SAS) AF: 0.834 AC: 4028 AN: 4832

European-Finnish (FIN) AF: 0.695 AC: 7363 AN: 10590

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52907 AN: 68022

Other (OTH) AF: 0.763 AC: 1613 AN: 2114

Alfa AF: 0.763 Hom.: 154874

Bravo AF: 0.737

Asia WGS AF: 0.743 AC: 2585 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	5.0
DANN	Benign	0.66
PhyloP100		-0.0040
PromoterAI		-0.070	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: rs7248363; hg19: chr19-18467886;