rs8114671

Positions:

• chr20-35201339-C-A
• chr20-35201339-C-G

Variant summary

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

The NM_001355008.2(MMP24-AS1-EDEM2):​c.-102+16473G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,998 control chromosomes in the GnomAD database, including 13,303 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 0.41 (13303 hom., cov: 32)
• Consequence: MMP24-AS1-EDEM2 NM_001355008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

Genes affected

MMP24-AS1-EDEM2 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP24-AS1-EDEM2	NM_001355008.2	c.-102+16473G>T		intron_variant			NP_001341937.1
PROCR	XM_011528496.2	c.713-14554C>A		intron_variant			XP_011526798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROCR	ENST00000635377.1	c.629-14554C>A		intron_variant		5		ENSP00000489117.1
PROCR	ENST00000634509.1	c.95-14554C>A		intron_variant		3		ENSP00000489456.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61767 AN: 151882 Hom.: 13299 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.432

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.406 AC: 61773 AN: 151998 Hom.: 13303 Cov.: 32 AF XY: 0.406 AC XY: 30147 AN XY: 74278

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.427

Alfa AF: 0.268 Hom.: 634

Bravo AF: 0.417

Asia WGS AF: 0.415 AC: 1443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8114671; hg19: chr20-33789142;