Genetic Variant PRCP:c.169-10428G>C (chr11-82870545-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005040.4(PRCP):c.169-10428G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0462 in 152,154 control chromosomes in the GnomAD database, including 246 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 0.046 ( 246 hom., cov: 32)

Consequence

PRCP
NM_005040.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.82

Publications

3 publications found

Variant links:

Genes affected

PRCP (HGNC:9344): (prolylcarboxypeptidase) This gene encodes a member of the peptidase S28 family of serine exopeptidases. The encoded preproprotein is proteolytically processed to generate the mature lysosomal prolylcarboxypeptidase. This enzyme cleaves C-terminal amino acids linked to proline in peptides such as angiotension II, III and des-Arg9-bradykinin. The cleavage occurs at acidic pH, but the enzyme activity is retained with some substrates at neutral pH. This enzyme has been shown to be an activator of the cell matrix-associated prekallikrein. The importance of angiotension II, one of the substrates of this enzyme, in regulating blood pressure and electrolyte balance suggests that this gene may be related to essential hypertension. A pseudogene of this gene has been identified on chromosome 2. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

PRCP 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRCP	NM_005040.4 link	c.169-10428G>C	intron_variant	Intron 1 of 8	ENST00000313010.8	NP_005031.1	P42785-1A0A024R5L0
PRCP	NM_199418.4 link	c.232-10428G>C	intron_variant	Intron 2 of 9		NP_955450.2	P42785-2
PRCP	NM_001319214.2 link	c.-6-17267G>C	intron_variant	Intron 1 of 7		NP_001306143.1	P42785B7Z7Q6
PRCP	XM_005274093.2 link	c.-147-10428G>C	intron_variant	Intron 1 of 8		XP_005274150.1	B7Z7Q6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRCP	ENST00000313010.8 link	c.169-10428G>C		intron_variant	Intron 1 of 8	1	NM_005040.4	ENSP00000317362.3		P42785-1

Frequencies

GnomAD3 genomes

AF:

0.0461

AC:

7012

AN:

152034

Hom.:

241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0173

Gnomad AMI

AF:

0.108

Gnomad AMR

AF:

0.0348

Gnomad ASJ

AF:

0.0332

Gnomad EAS

AF:

0.0886

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.0683

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0542

Gnomad OTH

AF:

0.0517

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

GnomAD4 genome

AF:

0.0462

AC:

7028

AN:

152154

Hom.:

246

Cov.:

AF XY:

0.0469

AC XY:

3490

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.0172

AC:

716

AN:

41512

American (AMR)

AF:

0.0347

AC:

531

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0332

AC:

115

AN:

3468

East Asian (EAS)

AF:

0.0886

AC:

458

AN:

5172

South Asian (SAS)

AF:

0.117

AC:

564

AN:

4818

European-Finnish (FIN)

AF:

0.0683

AC:

723

AN:

10590

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0542

AC:

3687

AN:

67992

Other (OTH)

AF:

0.0578

AC:

122

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

343

687

1030

1374

1717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.00899

Hom.:

Bravo

AF:

0.0417

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.087

(source)

DANN

Benign

0.53

PhyloP100

-1.8

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over