rs7226
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000269919.11(PGPEP1):c.*6216C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000908 in 151,986 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00091 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PGPEP1
ENST00000269919.11 3_prime_UTR
ENST00000269919.11 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.262
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PGPEP1 | NM_017712.4 | c.*6216C>A | 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.*6216C>A | 3_prime_UTR_variant | 5/5 | 1 | NM_017712.4 | ENSP00000269919 | P1 | ||
PGPEP1 | ENST00000597663.2 | c.234C>A | p.Pro78= | synonymous_variant | 2/2 | 3 | ENSP00000473226 | |||
PGPEP1 | ENST00000595552.2 | c.*5C>A | 3_prime_UTR_variant | 3/3 | 2 | ENSP00000471130 |
Frequencies
GnomAD3 genomes AF: 0.000915 AC: 139AN: 151868Hom.: 0 Cov.: 31
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 54Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 44
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GnomAD4 genome AF: 0.000908 AC: 138AN: 151986Hom.: 0 Cov.: 31 AF XY: 0.000835 AC XY: 62AN XY: 74268
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ClinVar
Not reported inComputational scores
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Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at