rs11167260

Variant names:

• chr20-35187397-G-A
• rs11167260
• NM_001355008.2:c.-101-21526C>T

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.-101-21526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 152,178 control chromosomes in the GnomAD database, including 731 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 0.092 (731 hom., cov: 32)
• Consequence: MMP24-AS1-EDEM2 NM_001355008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• Publications: 23 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP24-AS1-EDEM2	NM_001355008.2	c.-101-21526C>T		intron_variant	Intron 4 of 14		NP_001341937.1
PROCR	XM_011528496.2	c.712+10951G>A		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+10182G>A		intron_variant	Intron 3 of 3	5		ENSP00000489117.1
PROCR	ENST00000634509.1	c.94+10951G>A		intron_variant	Intron 1 of 1	3		ENSP00000489456.1

Frequencies

GnomAD3 genomes AF: 0.0916 AC: 13924 AN: 152060 Hom.: 720 Cov.: 32

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0750

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0962

Gnomad OTH AF: 0.0886

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

GnomAD4 genome AF: 0.0917 AC: 13959 AN: 152178 Hom.: 731 Cov.: 32 AF XY: 0.0953 AC XY: 7086 AN XY: 74386

African (AFR) AF: 0.0743 AC: 3087 AN: 41520

American (AMR) AF: 0.0677 AC: 1034 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3470

East Asian (EAS) AF: 0.0746 AC: 387 AN: 5186

South Asian (SAS) AF: 0.160 AC: 769 AN: 4820

European-Finnish (FIN) AF: 0.134 AC: 1419 AN: 10570

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0962 AC: 6541 AN: 68012

Other (OTH) AF: 0.0924 AC: 195 AN: 2110

Alfa AF: 0.0925 Hom.: 1033

Bravo AF: 0.0832

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.76
PhyloP100		0.29
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: rs11167260; hg19: chr20-33775200;