20-35191465-A-T

Variant names:

• chr20-35191465-A-T
• rs663550
• NM_001355008.2:c.-101-25594T>A

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.-101-25594T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,492 control chromosomes in the GnomAD database, including 12,422 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 0.39 (12422 hom., cov: 31)
• Consequence: MMP24-AS1-EDEM2 NM_001355008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP24-AS1-EDEM2	NM_001355008.2	c.-101-25594T>A		intron_variant	Intron 4 of 14		NP_001341937.1
PROCR	XM_011528496.2	c.712+15019A>T		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+14250A>T		intron_variant	Intron 3 of 3	5		ENSP00000489117.1
PROCR	ENST00000634509.1	c.94+15019A>T		intron_variant	Intron 1 of 1	3		ENSP00000489456.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58334 AN: 151374 Hom.: 12419 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.385 AC: 58342 AN: 151492 Hom.: 12422 Cov.: 31 AF XY: 0.386 AC XY: 28572 AN XY: 73976

African (AFR) AF: 0.197 AC: 8135 AN: 41310

American (AMR) AF: 0.516 AC: 7848 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1380 AN: 3448

East Asian (EAS) AF: 0.643 AC: 3308 AN: 5148

South Asian (SAS) AF: 0.344 AC: 1651 AN: 4802

European-Finnish (FIN) AF: 0.430 AC: 4493 AN: 10446

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30047 AN: 67822

Other (OTH) AF: 0.416 AC: 875 AN: 2104

Alfa AF: 0.252 Hom.: 585

Bravo AF: 0.392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.7
DANN	Benign	0.62
PhyloP100		-0.22
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: rs663550; hg19: chr20-33779268;