Genetic Variant MMP24-AS1-EDEM2:c.-102+16473G>T (chr20-35201339-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.41

Publications

23 publications found

Variant links:

Genes affected

MMP24-AS1-EDEM2 (HGNC:):

MMP24-AS1-EDEM2 links:

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]

PROCR links:

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new If you want to explore the variant's impact on the transcript NM_001355008.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

BA1

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	N/A	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	N/A	ENSP00000489117.1	A0A0U1RQQ4
	PROCR	ENST00000634509.1	TSL:3	c.95-14554C>A		intron	N/A	ENSP00000489456.1	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	0.407	61767	13299	151882	32
GnomAD4 genome	0.406	61773	13303	151998	32
TOPMed (Bravo)	0.417	110422	24741	264690
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	0.417	91666	20360	219828
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	0.467	1094	276	2342
ChinaMAP Phase 1	0.654
Denmark Genome	0.447	134		300
GenomeAsia100K	0.415	1443		3478
Korea4K (4,157 Koreans)	0.694	5018		7226
Qatari Genome	0.330	58		176
ToMMo 61KJPN (+60KJPN MNV)	0.728	89285	32613	122694
Turkish Variome	0.409	632	135	1546
UK10K	0.446	3375		7562
WBBC (Westlake BioBank for Chinese) pilot	0.634	5682	1810	8960

Showing 14 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
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	polymorphism (auto)	100/0
PhyloP100	Benign	-	-1.4

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over