20-35201339-C-A

Variant names:

• chr20-35201339-C-A
• rs8114671
• NM_001355008.2:c.-102+16473G>T

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_001355008.2(MMP24-AS1-EDEM2):c.-102+16473G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: NM_001355008.2 is not a MANE Select or MANE Plus Clinical transcript for MMP24-AS1-EDEM2; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.406 (AC=61,773) in the gnomAD database across 151,998 control chromosomes, including 13,303 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.621. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13303 hom., cov: 32)
• Consequence: MMP24-AS1-EDEM2 NM_001355008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 24 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]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6215 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MMP24-AS1-EDEM2 NM_001355008.2		c.-102+16473G>T	intron	Intron 4 of 14	Prot: NP_001341937.1

MMP24-AS1-EDEM2 NM_001355008.2

HGVSc / HGVSpc.-102+16473G>T

Exon rankIntron 4 of 14

intron

Prot: NP_001341937.1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PROCR ENST00000635377.1	TSL:5	c.629-14554C>A	intron	Intron 3 of 3	Prot: ENSP00000489117.1 UniProt:
	PROCR ENST00000634509.1	TSL:3	c.95-14554C>A	intron	Intron 1 of 1	Prot: ENSP00000489456.1 UniProt:

PROCR ENST00000635377.1

TSL:5

HGVSc / HGVSpc.629-14554C>A

Exon rankIntron 3 of 3

intron

Prot: ENSP00000489117.1UniProt: A0A0U1RQQ4

PROCR ENST00000634509.1

TSL:3

HGVSc / HGVSpc.95-14554C>A

Exon rankIntron 1 of 1

intron

Prot: ENSP00000489456.1UniProt: A0A0U1RRC4

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.407	AC:61767	Hom:13299	AN:151882	Cov:32
GnomAD4 genome	AF: 0.406	AC:61773	Hom:13303	AN:151998	Cov:32
TOPMed (Bravo)	AF: 0.417	AC:110422	Hom:24741	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.417	AC:91666	Hom:20360	AN:219828	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.467	AC:1094	Hom:276	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.654	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.447	AC:134	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.415	AC:1443	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.694	AC:5018	Hom:	AN:7226	Cov:
Qatari Genome	AF: 0.330	AC:58	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.728	AC:89285	Hom:32613	AN:122694	Cov:
Turkish Variome	AF: 0.409	AC:632	Hom:135	AN:1546	Cov:
UK10K	AF: 0.446	AC:3375	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.634	AC:5682	Hom:1810	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.30
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.37
GPN-Star LLR	N/A	2.6
GPN-Star score	N/A	-2.1
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-1.4

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0

Showing 1 of 1 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs8114671;

hg19: chr20-33789142;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar