rs11167260

Positions:

• chr20-35187397-G-A

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.-101-21526C>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

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=-0.82).
• 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/exons	MANE	UniProt
MMP24-AS1-EDEM2	NM_001355008.2	c.-101-21526C>T		intron_variant
PROCR	XM_011528496.2	c.712+10951G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROCR	ENST00000634509.1	c.94+10951G>A		intron_variant		3
PROCR	ENST00000635377.1	c.630+10182G>A		intron_variant		5

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

Gnomad4 AFR AF: 0.0743

Gnomad4 AMR AF: 0.0677

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0746

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0962

Gnomad4 OTH AF: 0.0924

Alfa AF: 0.0930 Hom.: 739

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11167260; hg19: chr20-33775200;