rs7104980

Positions:

• chr11-82864153-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.169-4036G>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 NM_005040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRCP	NM_005040.4	c.169-4036G>C		intron_variant		ENST00000313010.8	NP_005031.1
PRCP	NM_001319214.2	c.-6-10875G>C		intron_variant			NP_001306143.1
PRCP	NM_199418.4	c.232-4036G>C		intron_variant			NP_955450.2
PRCP	XM_005274093.2	c.-147-4036G>C		intron_variant			XP_005274150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRCP	ENST00000313010.8	c.169-4036G>C		intron_variant		1	NM_005040.4	ENSP00000317362	P1

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

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.521

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.57

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: rs7104980; hg19: chr11-82575195;