Genetic Variant MMP12:c.1205+88A>G (chr11-102865688-T-C) – 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.1205+88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 1,104,076 control chromosomes in the GnomAD database, including 3,618 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 0.11 ( 1355 hom., cov: 32)

Exomes 𝑓: 0.058 ( 2263 hom. )

Consequence

MMP12
NM_002426.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

13 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:

LOC124902741 (HGNC:):

LOC124902741 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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP12	NM_002426.6 link	c.1205+88A>G		intron_variant	Intron 8 of 9	ENST00000571244.3	NP_002417.2	P39900
LOC124902741	XR_007062868.1 link	n.2482T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3 link	c.1205+88A>G		intron_variant	Intron 8 of 9	1	NM_002426.6	ENSP00000458585.1		P39900

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16514

AN:

152006

Hom.:

1350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.0742

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0996

Gnomad FIN

AF:

0.0406

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.0529

Gnomad OTH

AF:

0.107

GnomAD4 exome

AF:

0.0575

AC:

54747

AN:

951952

Hom.:

2263

AF XY:

0.0584

AC XY:

27730

AN XY:

474556

show subpopulations

African (AFR)

AF:

0.234

AC:

5117

AN:

21884

American (AMR)

AF:

0.0525

AC:

1076

AN:

20500

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

2105

AN:

17508

East Asian (EAS)

AF:

0.0797

AC:

2653

AN:

33284

South Asian (SAS)

AF:

0.0923

AC:

4417

AN:

47830

European-Finnish (FIN)

AF:

0.0416

AC:

1505

AN:

36160

Middle Eastern (MID)

AF:

0.140

AC:

600

AN:

4290

European-Non Finnish (NFE)

AF:

0.0466

AC:

33940

AN:

728192

Other (OTH)

AF:

0.0788

AC:

3334

AN:

42304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2421

4843

7264

9686

12107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1280

2560

3840

5120

6400

<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:

0.109

AC:

16520

AN:

152124

Hom.:

1355

Cov.:

AF XY:

0.107

AC XY:

7925

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.229

AC:

9492

AN:

41468

American (AMR)

AF:

0.0740

AC:

1131

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

443

AN:

3466

East Asian (EAS)

AF:

0.110

AC:

569

AN:

5180

South Asian (SAS)

AF:

0.0985

AC:

475

AN:

4824

European-Finnish (FIN)

AF:

0.0406

AC:

430

AN:

10598

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0528

AC:

3593

AN:

67986

Other (OTH)

AF:

0.111

AC:

234

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

721

1443

2164

2886

3607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0665

Hom.:

724

Bravo

AF:

0.116

Asia WGS

AF:

0.113

AC:

393

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.5

(source)

DANN

Benign

0.37

PhyloP100

-1.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over