dbSNP rs632009: MMP12:c.787+140G>A (chr11-102867768-C-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.787+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 864,874 control chromosomes in the GnomAD database, including 43,661 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 0.24 ( 5433 hom., cov: 32)

Exomes 𝑓: 0.32 ( 38228 hom. )

Consequence

MMP12
NM_002426.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.22

Publications

8 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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP12	NM_002426.6 link	c.787+140G>A		intron_variant	Intron 5 of 9	ENST00000571244.3	NP_002417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3 link	c.787+140G>A		intron_variant	Intron 5 of 9	1	NM_002426.6	ENSP00000458585.1

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36652

AN:

151834

Hom.:

5429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0673

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.261

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.0972

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.248

GnomAD4 exome

AF:

0.319

AC:

227303

AN:

712922

Hom.:

38228

AF XY:

0.322

AC XY:

117435

AN XY:

364292

show subpopulations

African (AFR)

AF:

0.0627

AC:

1075

AN:

17146

American (AMR)

AF:

0.256

AC:

5985

AN:

23414

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

3874

AN:

16104

East Asian (EAS)

AF:

0.124

AC:

3996

AN:

32294

South Asian (SAS)

AF:

0.398

AC:

20432

AN:

51322

European-Finnish (FIN)

AF:

0.305

AC:

10855

AN:

35562

Middle Eastern (MID)

AF:

0.237

AC:

741

AN:

3120

European-Non Finnish (NFE)

AF:

0.341

AC:

170281

AN:

499308

Other (OTH)

AF:

0.290

AC:

10064

AN:

34652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

7407

14814

22220

29627

37034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3836

7672

11508

15344

19180

<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:

0.241

AC:

36651

AN:

151952

Hom.:

5433

Cov.:

AF XY:

0.241

AC XY:

17913

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.0672

AC:

2788

AN:

41490

American (AMR)

AF:

0.261

AC:

3971

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

835

AN:

3466

East Asian (EAS)

AF:

0.0976

AC:

506

AN:

5182

South Asian (SAS)

AF:

0.397

AC:

1908

AN:

4806

European-Finnish (FIN)

AF:

0.297

AC:

3122

AN:

10514

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22602

AN:

67938

Other (OTH)

AF:

0.246

AC:

520

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1357

2714

4072

5429

6786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.246

Hom.:

3301

Bravo

AF:

0.228

Asia WGS

AF:

0.219

AC:

762

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.3

(source)

DANN

Benign

0.58

PhyloP100

-1.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over