20-35180720-T-C

Position:

• chr20-35180720-T-C

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.-101-14849A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 152,226 control chromosomes in the GnomAD database, including 739 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 (739 hom., cov: 32)
• Consequence: MMP24-AS1-EDEM2 NM_001355008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506

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=-0.9).
• 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	Protein	UniProt
MMP24-AS1-EDEM2	NM_001355008.2	c.-101-14849A>G		intron_variant			NP_001341937.1
PROCR	XM_011528496.2	c.712+4274T>C		intron_variant			XP_011526798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROCR	ENST00000634509.1	c.94+4274T>C		intron_variant		3		ENSP00000489456
PROCR	ENST00000635377.1	c.630+3505T>C		intron_variant		5		ENSP00000489117

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13983 AN: 152108 Hom.: 728 Cov.: 32

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0681

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0759

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0964

Gnomad OTH AF: 0.0882

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

GnomAD4 genome AF: 0.0921 AC: 14019 AN: 152226 Hom.: 739 Cov.: 32 AF XY: 0.0956 AC XY: 7113 AN XY: 74426

Gnomad4 AFR AF: 0.0752

Gnomad4 AMR AF: 0.0678

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0755

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0964

Gnomad4 OTH AF: 0.0920

Alfa AF: 0.0905 Hom.: 142

Bravo AF: 0.0836

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	-0.90
CADD	Benign	11
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7265317; hg19: chr20-33768523;