rs7104980

Variant names:

• chr11-82864153-C-G
• rs7104980
• NM_005040.4:c.169-4036G>C

Variant summary

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

The ENST00000313010.8(PRCP):​c.169-4036G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,110 control chromosomes in the GnomAD database, including 20,491 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 0.51 (20491 hom., cov: 32)
• Consequence: PRCP ENST00000313010.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532
• Publications: 10 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 = 0.596 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000313010.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRCP	NM_005040.4	MANE Select	c.169-4036G>C		intron	N/A	NP_005031.1
	PRCP	NM_199418.4		c.232-4036G>C		intron	N/A	NP_955450.2
	PRCP	NM_001319214.2		c.-6-10875G>C		intron	N/A	NP_001306143.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRCP	ENST00000313010.8	TSL:1 MANE Select	c.169-4036G>C		intron	N/A	ENSP00000317362.3
	PRCP	ENST00000393399.6	TSL:2	c.232-4036G>C		intron	N/A	ENSP00000377055.2
	PRCP	ENST00000532809.2	TSL:3	c.7-4036G>C		intron	N/A	ENSP00000437169.2

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78087 AN: 151992 Hom.: 20465 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.514 AC: 78163 AN: 152110 Hom.: 20491 Cov.: 32 AF XY: 0.511 AC XY: 37998 AN XY: 74360

African (AFR) AF: 0.602 AC: 24991 AN: 41492

American (AMR) AF: 0.549 AC: 8395 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1732 AN: 3468

East Asian (EAS) AF: 0.292 AC: 1512 AN: 5182

South Asian (SAS) AF: 0.456 AC: 2202 AN: 4824

European-Finnish (FIN) AF: 0.486 AC: 5140 AN: 10568

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32559 AN: 67974

Other (OTH) AF: 0.521 AC: 1098 AN: 2108

Alfa AF: 0.508 Hom.: 2447

Bravo AF: 0.523

Asia WGS AF: 0.433 AC: 1505 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	0.55
DANN	Benign	0.57
PhyloP100		-0.53
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: rs7104980; hg19: chr11-82575195;