rs1415774

Variant names:

• chr20-35177813-A-G
• rs1415774
• NM_001355008.2:c.-101-11942T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MMP24-AS1-EDEM2	NM_001355008.2	c.-101-11942T>C		intron_variant	Intron 4 of 14		NP_001341937.1
PROCR	XM_011528496.2	c.712+1367A>G		intron_variant	Intron 4 of 4		XP_011526798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROCR	ENST00000635377.1	c.628+598A>G		intron_variant	Intron 3 of 3	5		ENSP00000489117.1
PROCR	ENST00000634509.1	c.94+1367A>G		intron_variant	Intron 1 of 1	3		ENSP00000489456.1

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

African (AFR) AF: 0.803 AC: 33290 AN: 41448

American (AMR) AF: 0.485 AC: 7384 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2079 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1882 AN: 5154

South Asian (SAS) AF: 0.670 AC: 3229 AN: 4820

European-Finnish (FIN) AF: 0.568 AC: 5987 AN: 10542

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

European-Non Finnish (NFE) AF: 0.557 AC: 37851 AN: 67934

Other (OTH) AF: 0.585 AC: 1233 AN: 2106

Alfa AF: 0.580 Hom.: 48153

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
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1415774; hg19: chr20-33765616;