rs2069948

Variant names:

• chr20-35174686-C-T
• rs2069948
• NM_006404.5:c.71-16C>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.-101-8815G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,613,150 control chromosomes in the GnomAD database, including 267,694 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 0.62 (29946 hom., cov: 29)
  • Exomes 𝑓: 0.57 (237748 hom.)
• Consequence: MMP24-AS1-EDEM2 NM_001355008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325
• Publications: 41 publications found

Genes affected

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]

MMP24-AS1-EDEM2 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355008.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROCR	NM_006404.5	MANE Select	c.71-16C>T		intron	N/A	NP_006395.2
	MMP24-AS1-EDEM2	NM_001355008.2		c.-101-8815G>A		intron	N/A	NP_001341937.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROCR	ENST00000216968.5	TSL:1 MANE Select	c.71-16C>T		intron	N/A	ENSP00000216968.3
	PROCR	ENST00000852804.1		c.71-16C>T		intron	N/A	ENSP00000522863.1
	PROCR	ENST00000852805.1		c.71-16C>T		intron	N/A	ENSP00000522864.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93286 AN: 151694 Hom.: 29897 Cov.: 29

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.581

GnomAD2 exomes AF: 0.555 AC: 138411 AN: 249412 AF XY: 0.564

Gnomad AFR exome AF: 0.809

Gnomad AMR exome AF: 0.360

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.372

Gnomad FIN exome AF: 0.575

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.565 AC: 826046 AN: 1461338 Hom.: 237748 Cov.: 60 AF XY: 0.568 AC XY: 413226 AN XY: 726990

African (AFR) AF: 0.816 AC: 27336 AN: 33480

American (AMR) AF: 0.373 AC: 16701 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 15673 AN: 26130

East Asian (EAS) AF: 0.322 AC: 12777 AN: 39696

South Asian (SAS) AF: 0.677 AC: 58376 AN: 86250

European-Finnish (FIN) AF: 0.573 AC: 30397 AN: 53080

Middle Eastern (MID) AF: 0.592 AC: 3416 AN: 5766

European-Non Finnish (NFE) AF: 0.564 AC: 626681 AN: 1111832

Other (OTH) AF: 0.574 AC: 34689 AN: 60382

GnomAD4 genome AF: 0.615 AC: 93389 AN: 151812 Hom.: 29946 Cov.: 29 AF XY: 0.614 AC XY: 45598 AN XY: 74216

African (AFR) AF: 0.801 AC: 33189 AN: 41410

American (AMR) AF: 0.485 AC: 7385 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2077 AN: 3468

East Asian (EAS) AF: 0.357 AC: 1838 AN: 5152

South Asian (SAS) AF: 0.669 AC: 3223 AN: 4816

European-Finnish (FIN) AF: 0.569 AC: 5999 AN: 10546

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37850 AN: 67880

Other (OTH) AF: 0.587 AC: 1232 AN: 2100

Alfa AF: 0.582 Hom.: 40984

Bravo AF: 0.608

Asia WGS AF: 0.579 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		0.33
PromoterAI		-0.0026	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2069948; hg19: chr20-33762489; COSMIC: COSV53825740; COSMIC: COSV53825740;