11-82870545-C-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	UniProt
PRCP	NM_005040.4	c.169-10428G>C		intron_variant		ENST00000313010.8
PRCP	NM_001319214.2	c.-6-17267G>C		intron_variant
PRCP	NM_199418.4	c.232-10428G>C		intron_variant
PRCP	XM_005274093.2	c.-147-10428G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRCP	ENST00000313010.8	c.169-10428G>C		intron_variant		1	NM_005040.4	P1

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 7012 AN: 152034 Hom.: 241 Cov.: 32

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.: 32 AF XY: 0.0469 AC XY: 3490 AN XY: 74394

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.0347

Gnomad4 ASJ AF: 0.0332

Gnomad4 EAS AF: 0.0886

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0683

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.00899 Hom.: 2

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
Dann	Benign	0.53

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: rs3750929; hg19: chr11-82581587;