20-35176829-C-G

Position:

• chr20-35176829-C-G

Variant summary

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

The NM_006404.5(PROCR):​c.*16C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,610,788 control chromosomes in the GnomAD database, including 266,721 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 0.62 (29995 hom., cov: 30)
  • Exomes 𝑓: 0.56 (236726 hom.)
• Consequence: PROCR NM_006404.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.369

Genes affected

PROCR (HGNC:9452): (protein C receptor) The protein encoded by this gene is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The encoded protein is an N-glycosylated type I membrane protein that enhances the activation of protein C. Mutations in this gene have been associated with venous thromboembolism and myocardial infarction, as well as with late fetal loss during pregnancy. The encoded protein may also play a role in malarial infection and has been associated with cancer. [provided by RefSeq, Jul 2013]

MMP24-AS1-EDEM2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROCR	NM_006404.5	c.*16C>G		3_prime_UTR_variant	4/4	ENST00000216968.5
MMP24-AS1-EDEM2	NM_001355008.2	c.-101-10958G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROCR	ENST00000216968.5	c.*16C>G		3_prime_UTR_variant	4/4	1	NM_006404.5	P1
PROCR	ENST00000634509.1	c.94+383C>G		intron_variant		3
PROCR	ENST00000635377.1	c.502-258C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93335 AN: 151764 Hom.: 29940 Cov.: 30

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.579

GnomAD3 exomes AF: 0.554 AC: 136631 AN: 246476 Hom.: 39528 AF XY: 0.563 AC XY: 74961 AN XY: 133258

Gnomad AFR exome AF: 0.811

Gnomad AMR exome AF: 0.360

Gnomad ASJ exome AF: 0.596

Gnomad EAS exome AF: 0.373

Gnomad SAS exome AF: 0.676

Gnomad FIN exome AF: 0.574

Gnomad NFE exome AF: 0.566

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.565 AC: 823842 AN: 1458904 Hom.: 236726 Cov.: 60 AF XY: 0.568 AC XY: 411843 AN XY: 725428

Gnomad4 AFR exome AF: 0.818

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.598

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.673

Gnomad4 FIN exome AF: 0.572

Gnomad4 NFE exome AF: 0.563

Gnomad4 OTH exome AF: 0.574

GnomAD4 genome AF: 0.615 AC: 93445 AN: 151884 Hom.: 29995 Cov.: 30 AF XY: 0.614 AC XY: 45588 AN XY: 74194

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.584

Alfa AF: 0.512 Hom.: 2631

Bravo AF: 0.608

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs9574; hg19: chr20-33764632; COSMIC: COSV53825084; COSMIC: COSV53825084;