Genetic Variant MMP15:c.748+124A>G (chr16-58040306-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002428.4(MMP15):c.748+124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,091,612 control chromosomes in the GnomAD database, including 44,110 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 0.35 ( 11395 hom., cov: 33)

Exomes 𝑓: 0.25 ( 32715 hom. )

Consequence

MMP15
NM_002428.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

Publications

16 publications found

Variant links:

Genes affected

MMP15 (HGNC:7161): (matrix metallopeptidase 15) This gene encodes a member of the peptidase M10 family and membrane-type subfamily of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Members of this subfamily contain a transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. The encoded preproprotein is proteolytically processed to generate the mature protease. This protein may play a role in cancer progression. [provided by RefSeq, Jan 2016]

MMP15 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002428.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP15	NM_002428.4	MANE Select	c.748+124A>G		intron	N/A	NP_002419.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP15	ENST00000219271.4	TSL:1 MANE Select	c.748+124A>G		intron	N/A	ENSP00000219271.3
	MMP15	ENST00000570065.1	TSL:2	c.16+124A>G		intron	N/A	ENSP00000457084.1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53083

AN:

151992

Hom.:

11348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.596

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.367

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.370

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.284

GnomAD4 exome

AF:

0.251

AC:

235746

AN:

939502

Hom.:

32715

AF XY:

0.247

AC XY:

115621

AN XY:

468830

show subpopulations

African (AFR)

AF:

0.611

AC:

13350

AN:

21860

American (AMR)

AF:

0.430

AC:

9826

AN:

22836

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

2275

AN:

17330

East Asian (EAS)

AF:

0.380

AC:

12722

AN:

33464

South Asian (SAS)

AF:

0.214

AC:

12236

AN:

57288

European-Finnish (FIN)

AF:

0.317

AC:

9690

AN:

30540

Middle Eastern (MID)

AF:

0.130

AC:

481

AN:

3686

European-Non Finnish (NFE)

AF:

0.231

AC:

164372

AN:

710418

Other (OTH)

AF:

0.257

AC:

10794

AN:

42080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

9255

18510

27766

37021

46276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5282

10564

15846

21128

26410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.350

AC:

53199

AN:

152110

Hom.:

11395

Cov.:

AF XY:

0.352

AC XY:

26154

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.597

AC:

24774

AN:

41492

American (AMR)

AF:

0.367

AC:

5613

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

473

AN:

3472

East Asian (EAS)

AF:

0.371

AC:

1908

AN:

5146

South Asian (SAS)

AF:

0.221

AC:

1064

AN:

4824

European-Finnish (FIN)

AF:

0.319

AC:

3384

AN:

10594

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.223

AC:

15171

AN:

67982

Other (OTH)

AF:

0.285

AC:

602

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1588

3176

4765

6353

7941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.234

Hom.:

2708

Bravo

AF:

0.369

Asia WGS

AF:

0.345

AC:

1201

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.13

(source)

DANN

Benign

0.30

PhyloP100

-1.5

PromoterAI

0.016

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over