rs1043063

Positions:

• chr19-18369361-C-T

Variant summary

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

The NM_017712.4(PGPEP1):​c.*5778C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,270 control chromosomes in the GnomAD database, including 7,532 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 0.31 (7518 hom., cov: 31)
  • Exomes 𝑓: 0.29 (14 hom.)
• Consequence: PGPEP1 NM_017712.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.81

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGPEP1	NM_017712.4	c.*5778C>T		3_prime_UTR_variant	5/5	ENST00000269919.11	NP_060182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGPEP1	ENST00000269919.11	c.*5778C>T		3_prime_UTR_variant	5/5	1	NM_017712.4	ENSP00000269919	P1
PGPEP1	ENST00000595552.2	c.176-345C>T		intron_variant		2		ENSP00000471130
PGPEP1	ENST00000597663.2	c.139-345C>T		intron_variant		3		ENSP00000473226

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46747 AN: 151828 Hom.: 7516 Cov.: 31

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.293 AC: 95 AN: 324 Hom.: 14 Cov.: 0 AF XY: 0.269 AC XY: 63 AN XY: 234

Gnomad4 AFR exome AF: 0.286

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.308 AC: 46768 AN: 151946 Hom.: 7518 Cov.: 31 AF XY: 0.308 AC XY: 22893 AN XY: 74262

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.303

Alfa AF: 0.342 Hom.: 12939

Bravo AF: 0.293

Asia WGS AF: 0.327 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1043063; hg19: chr19-18480171;