rs2069948

chr20-35174686-C-T

Variant summary

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

The NM_006404.5(PROCR):c.71-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,613,150 control chromosomes in the GnomAD database, including 267,694 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 (29946 hom., cov: 29)
  • Exomes 𝑓: 0.57 (237748 hom.)
• Consequence: PROCR NM_006404.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROCR	NM_006404.5	c.71-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000216968.5
MMP24-AS1-EDEM2	NM_001355008.2	c.-101-8815G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROCR	ENST00000216968.5	c.71-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006404.5	P1
	ENST00000615962.1	n.234G>A		non_coding_transcript_exon_variant	1/1
PROCR	ENST00000635377.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93286 AN: 151694 Hom.: 29897 Cov.: 29

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.581

GnomAD3 exomes AF: 0.555 AC: 138411 AN: 249412 Hom.: 40352 AF XY: 0.564 AC XY: 76118 AN XY: 135030

Gnomad AFR exome AF: 0.809

Gnomad AMR exome AF: 0.360

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.372

Gnomad SAS exome AF: 0.680

Gnomad FIN exome AF: 0.575

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.565 AC: 826046 AN: 1461338 Hom.: 237748 Cov.: 60 AF XY: 0.568 AC XY: 413226 AN XY: 726990

Gnomad4 AFR exome AF: 0.816

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.600

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.677

Gnomad4 FIN exome AF: 0.573

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.574

GnomAD4 genome AF: 0.615 AC: 93389 AN: 151812 Hom.: 29946 Cov.: 29 AF XY: 0.614 AC XY: 45598 AN XY: 74216

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.587

Alfa AF: 0.598 Hom.: 5766

Bravo AF: 0.608

Asia WGS AF: 0.579 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	14
Dann	Benign	0.92

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: rs2069948; hg19: chr20-33762489; COSMIC: COSV53825740; COSMIC: COSV53825740;