rs9574

Positions:

• chr20-35176829-C-A
• chr20-35176829-C-G
• chr20-35176829-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006404.5(PROCR):​c.*16C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000561 in 1,611,156 control chromosomes in the GnomAD database, including 8 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 0.00043 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00057 (8 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000435 AC: 66 AN: 151848 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.00111 AC: 273 AN: 246476 Hom.: 0 AF XY: 0.00126 AC XY: 168 AN XY: 133258

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00151

Gnomad ASJ exome AF: 0.00311

Gnomad EAS exome AF: 0.0000554

Gnomad SAS exome AF: 0.00420

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000467

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.000574 AC: 838 AN: 1459188 Hom.: 8 Cov.: 60 AF XY: 0.000670 AC XY: 486 AN XY: 725580

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00138

Gnomad4 ASJ exome AF: 0.00211

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00387

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000222

Gnomad4 OTH exome AF: 0.000978

GnomAD4 genome AF: 0.000434 AC: 66 AN: 151968 Hom.: 0 Cov.: 30 AF XY: 0.000472 AC XY: 35 AN XY: 74228

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000851

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00291

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.000950

Alfa AF: 0.00122 Hom.: 2631

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.6
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;