20-35176829-C-G

Variant names:

• chr20-35176829-C-G
• rs9574
• NM_006404.5:c.*16C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 45 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PROCR	NM_006404.5	c.*16C>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000216968.5	NP_006395.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROCR	ENST00000216968.5	c.*16C>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_006404.5	ENSP00000216968.3
PROCR	ENST00000635377.1	c.500-258C>G		intron_variant	Intron 2 of 3	5		ENSP00000489117.1
PROCR	ENST00000634509.1	c.94+383C>G		intron_variant	Intron 1 of 1	3		ENSP00000489456.1

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

GnomAD2 exomes AF: 0.554 AC: 136631 AN: 246476 AF XY: 0.563

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 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

African (AFR) AF: 0.818 AC: 27366 AN: 33466

American (AMR) AF: 0.373 AC: 16488 AN: 44194

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 15573 AN: 26052

East Asian (EAS) AF: 0.323 AC: 12795 AN: 39650

South Asian (SAS) AF: 0.673 AC: 57698 AN: 85728

European-Finnish (FIN) AF: 0.572 AC: 30439 AN: 53212

Middle Eastern (MID) AF: 0.581 AC: 3348 AN: 5760

European-Non Finnish (NFE) AF: 0.563 AC: 625537 AN: 1110534

Other (OTH) AF: 0.574 AC: 34598 AN: 60308

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

African (AFR) AF: 0.803 AC: 33282 AN: 41428

American (AMR) AF: 0.484 AC: 7387 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2076 AN: 3470

East Asian (EAS) AF: 0.358 AC: 1844 AN: 5146

South Asian (SAS) AF: 0.666 AC: 3203 AN: 4806

European-Finnish (FIN) AF: 0.569 AC: 5989 AN: 10524

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37836 AN: 67942

Other (OTH) AF: 0.584 AC: 1230 AN: 2106

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
PhyloP100		0.37
PromoterAI		0.0065	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9574; hg19: chr20-33764632; COSMIC: COSV53825084; COSMIC: COSV53825084;