20-35171469-C-G

Variant names:

• chr20-35171469-C-G
• rs2069940
• NM_001355008.2:c.-101-5598G>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.-101-5598G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 152,128 control chromosomes in the GnomAD database, including 634 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 0.083 (634 hom., cov: 32)
• Consequence: MMP24-AS1-EDEM2 NM_001355008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP24-AS1-EDEM2	NM_001355008.2	c.-101-5598G>C		intron_variant	Intron 4 of 14		NP_001341937.1
PROCR	XM_047439830.1	c.45+250C>G		intron_variant	Intron 1 of 4		XP_047295786.1
PROCR	XM_011528496.2	c.45+250C>G		intron_variant	Intron 1 of 4		XP_011526798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12564 AN: 152010 Hom.: 631 Cov.: 32

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.0848

Gnomad AMR AF: 0.0639

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0728

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0962

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.0826 AC: 12566 AN: 152128 Hom.: 634 Cov.: 32 AF XY: 0.0860 AC XY: 6395 AN XY: 74374

African (AFR) AF: 0.0432 AC: 1792 AN: 41508

American (AMR) AF: 0.0637 AC: 972 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 425 AN: 3462

East Asian (EAS) AF: 0.0724 AC: 375 AN: 5182

South Asian (SAS) AF: 0.157 AC: 758 AN: 4814

European-Finnish (FIN) AF: 0.135 AC: 1423 AN: 10570

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0962 AC: 6543 AN: 68008

Other (OTH) AF: 0.0848 AC: 179 AN: 2112

Alfa AF: 0.0905 Hom.: 89

Bravo AF: 0.0729

Asia WGS AF: 0.127 AC: 441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.5
DANN	Benign	0.40
PhyloP100		0.0010
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: rs2069940; hg19: chr20-33759272;