chr19-18357076-T-C

Position:

• chr19-18357076-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PGPEP1	NM_017712.4	c.205-307T>C		intron_variant		ENST00000269919.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGPEP1	ENST00000269919.11	c.205-307T>C		intron_variant		1	NM_017712.4	P1

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

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.818

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.834

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.763

Alfa AF: 0.769 Hom.: 64446

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

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: rs7248363; hg19: chr19-18467886;