dbSNP rs1043063: PGPEP1:c.*5778C>T (chr19-18369361-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.81

Publications

15 publications found

Variant links:

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]

PGPEP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PGPEP1	NM_017712.4 link	c.*5778C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000269919.11	NP_060182.1	Q9NXJ5-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PGPEP1	ENST00000269919.11 link	c.*5778C>T	3_prime_UTR_variant	Exon 5 of 5	1	NM_017712.4	ENSP00000269919.3	Q9NXJ5-1
PGPEP1	ENST00000597663.2 link	c.138-345C>T	intron_variant	Intron 1 of 1	3		ENSP00000473226.2	M0R3H3
PGPEP1	ENST00000595552.2 link	c.176-345C>T	intron_variant	Intron 2 of 2	2		ENSP00000471130.2	M0R0B6

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46747

AN:

151828

Hom.:

7516

Cov.:

show subpopulations

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:

AN:

324

Hom.:

Cov.:

AF XY:

0.269

AC XY:

AN XY:

234

show subpopulations

African (AFR)

AF:

0.286

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.200

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.318

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.289

AC:

AN:

256

Other (OTH)

AF:

0.444

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.308

AC:

46768

AN:

151946

Hom.:

7518

Cov.:

AF XY:

0.308

AC XY:

22893

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.224

AC:

9291

AN:

41438

American (AMR)

AF:

0.254

AC:

3870

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1205

AN:

3468

East Asian (EAS)

AF:

0.281

AC:

1447

AN:

5152

South Asian (SAS)

AF:

0.402

AC:

1937

AN:

4816

European-Finnish (FIN)

AF:

0.372

AC:

3934

AN:

10566

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.353

AC:

23986

AN:

67942

Other (OTH)

AF:

0.303

AC:

638

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1663

3326

4990

6653

8316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.337

Hom.:

17291

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

(source)

DANN

Benign

0.55

PhyloP100

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over