Genetic Variant MMP12:c.351-79C>A (chr11-102872031-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002426.6(MMP12):c.351-79C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,377,676 control chromosomes in the GnomAD database, including 10,567 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 0.095 ( 982 hom., cov: 32)

Exomes 𝑓: 0.12 ( 9585 hom. )

Consequence

MMP12
NM_002426.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.154

Publications

24 publications found

Variant links:

Genes affected

MMP12 (HGNC:7158): (matrix metallopeptidase 12) This gene encodes a member of the peptidase M10 family 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. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease degrades soluble and insoluble elastin. This gene may play a role in aneurysm formation and mutations in this gene are associated with lung function and chronic obstructive pulmonary disease (COPD). This gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

MMP12 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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002426.6. 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
	MMP12	NM_002426.6	MANE Select	c.351-79C>A		intron	N/A	NP_002417.2	P39900

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP12	ENST00000571244.3	TSL:1 MANE Select	c.351-79C>A		intron	N/A	ENSP00000458585.1	P39900

Frequencies

GnomAD3 genomes

AF:

0.0955

AC:

14530

AN:

152104

Hom.:

981

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0253

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0720

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.0264

Gnomad SAS

AF:

0.0800

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.0953

GnomAD4 exome

AF:

0.120

AC:

147459

AN:

1225452

Hom.:

9585

AF XY:

0.120

AC XY:

71703

AN XY:

598632

show subpopulations

African (AFR)

AF:

0.0207

AC:

565

AN:

27306

American (AMR)

AF:

0.0594

AC:

1136

AN:

19138

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

2490

AN:

18598

East Asian (EAS)

AF:

0.0254

AC:

909

AN:

35794

South Asian (SAS)

AF:

0.0881

AC:

4958

AN:

56276

European-Finnish (FIN)

AF:

0.190

AC:

8493

AN:

44772

Middle Eastern (MID)

AF:

0.147

AC:

743

AN:

5062

European-Non Finnish (NFE)

AF:

0.127

AC:

122451

AN:

967274

Other (OTH)

AF:

0.112

AC:

5714

AN:

51232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

6139

12277

18416

24554

30693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4444

8888

13332

17776

22220

<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:

0.0955

AC:

14532

AN:

152224

Hom.:

982

Cov.:

AF XY:

0.0973

AC XY:

7244

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0252

AC:

1047

AN:

41544

American (AMR)

AF:

0.0719

AC:

1101

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

417

AN:

3468

East Asian (EAS)

AF:

0.0264

AC:

137

AN:

5186

South Asian (SAS)

AF:

0.0809

AC:

390

AN:

4820

European-Finnish (FIN)

AF:

0.214

AC:

2260

AN:

10580

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.130

AC:

8838

AN:

68006

Other (OTH)

AF:

0.0934

AC:

197

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

659

1317

1976

2634

3293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.116

Hom.:

2214

Bravo

AF:

0.0818

Asia WGS

AF:

0.0590

AC:

207

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.9

(source)

DANN

Benign

0.51

PhyloP100

0.15

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