11-82874314-G-T

Variant names:

• chr11-82874314-G-T
• rs2086297
• NM_005040.4:c.169-14197C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005040.4(PRCP):​c.169-14197C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,156 control chromosomes in the GnomAD database, including 1,584 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 0.11 (1584 hom., cov: 32)
• Consequence: PRCP NM_005040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005040.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRCP	NM_005040.4	MANE Select	c.169-14197C>A		intron	N/A	NP_005031.1
	PRCP	NM_199418.4		c.231+10509C>A		intron	N/A	NP_955450.2
	PRCP	NM_001319214.2		c.-6-21036C>A		intron	N/A	NP_001306143.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRCP	ENST00000313010.8	TSL:1 MANE Select	c.169-14197C>A		intron	N/A	ENSP00000317362.3
	PRCP	ENST00000393399.6	TSL:2	c.231+10509C>A		intron	N/A	ENSP00000377055.2
	PRCP	ENST00000949391.1		c.169-14197C>A		intron	N/A	ENSP00000619450.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16738 AN: 152038 Hom.: 1578 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.0889

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.110 AC: 16782 AN: 152156 Hom.: 1584 Cov.: 32 AF XY: 0.109 AC XY: 8133 AN XY: 74390

African (AFR) AF: 0.257 AC: 10645 AN: 41486

American (AMR) AF: 0.123 AC: 1888 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3470

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5188

South Asian (SAS) AF: 0.0890 AC: 428 AN: 4810

European-Finnish (FIN) AF: 0.0399 AC: 423 AN: 10590

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0453 AC: 3078 AN: 68006

Other (OTH) AF: 0.100 AC: 212 AN: 2112

Alfa AF: 0.0604 Hom.: 799

Bravo AF: 0.122

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.51
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2086297; hg19: chr11-82585356;