11-82874314-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRCP	NM_005040.4	c.169-14197C>A		intron_variant	Intron 1 of 8	ENST00000313010.8	NP_005031.1
PRCP	NM_199418.4	c.231+10509C>A		intron_variant	Intron 2 of 9		NP_955450.2
PRCP	NM_001319214.2	c.-6-21036C>A		intron_variant	Intron 1 of 7		NP_001306143.1
PRCP	XM_005274093.2	c.-147-14197C>A		intron_variant	Intron 1 of 8		XP_005274150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRCP	ENST00000313010.8	c.169-14197C>A		intron_variant	Intron 1 of 8	1	NM_005040.4	ENSP00000317362.3

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

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0890

Gnomad4 FIN AF: 0.0399

Gnomad4 NFE AF: 0.0453

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0523 Hom.: 436

Bravo AF: 0.122

Asia WGS AF: 0.0780 AC: 271 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	0.36
DANN	Benign	0.51

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: rs2086297; hg19: chr11-82585356;