rs1415774

Positions:

• chr20-35177813-A-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.-101-11942T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,914 control chromosomes in the GnomAD database, including 30,025 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 (30025 hom., cov: 30)
• Consequence: MMP24-AS1-EDEM2 NM_001355008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.697

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=-0.88).
• 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
MMP24-AS1-EDEM2	NM_001355008.2	c.-101-11942T>C		intron_variant
PROCR	XM_011528496.2	c.712+1367A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROCR	ENST00000634509.1	c.94+1367A>G		intron_variant		3
PROCR	ENST00000635377.1	c.630+598A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93420 AN: 151796 Hom.: 29970 Cov.: 30

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.616 AC: 93530 AN: 151914 Hom.: 30025 Cov.: 30 AF XY: 0.615 AC XY: 45644 AN XY: 74242

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.585

Alfa AF: 0.564 Hom.: 10195

Bravo AF: 0.609

Asia WGS AF: 0.580 AC: 2019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1415774; hg19: chr20-33765616;