11-102796715-CA-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_002421.4(MMP1):c.573delT(p.Ile191MetfsTer45) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,990 control chromosomes in the GnomAD database, including 183 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.011 ( 10 hom., cov: 33)

Exomes 𝑓: 0.014 ( 173 hom. )

Consequence

MMP1
NM_002421.4 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.48

Publications

12 publications found

Variant links:

Genes affected

MMP1 (HGNC:7155): (matrix metallopeptidase 1) 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 secreted protease breaks down the interstitial collagens, including types I, II, and III. The gene is part of a cluster of MMP genes on chromosome 11. Mutations in this gene are associated with chronic obstructive pulmonary disease (COPD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

MMP1 links:

WTAPP1 (HGNC:):

WTAPP1 links:

WTAPP1 (HGNC:44115): (WTAP pseudogene 1)

WTAPP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 11-102796715-CA-C is Benign according to our data. Variant chr11-102796715-CA-C is described in CliVar as Benign. Clinvar id is 2642324.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-102796715-CA-C is described in CliVar as Benign. Clinvar id is 2642324.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-102796715-CA-C is described in CliVar as Benign. Clinvar id is 2642324.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0112 (1699/152310) while in subpopulation NFE AF = 0.0187 (1269/68024). AF 95% confidence interval is 0.0178. There are 10 homozygotes in GnomAd4. There are 798 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4 link	c.573delT	p.Ile191MetfsTer45	frameshift_variant	Exon 4 of 10	ENST00000315274.7	NP_002412.1	P03956Q53G95
MMP1	NM_001145938.2 link	c.375delT	p.Ile125MetfsTer45	frameshift_variant	Exon 4 of 10		NP_001139410.1	B4DN15
WTAPP1	NR_038390.1 link	n.584-1307delA		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7 link	c.573delT	p.Ile191MetfsTer45	frameshift_variant	Exon 4 of 10	1	NM_002421.4	ENSP00000322788.6		P03956

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1699

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00903

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0187

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.0114

AC:

2867

AN:

251148

AF XY:

0.0119

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00643

Gnomad ASJ exome

AF:

0.00417

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.0172

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.0136

AC:

19913

AN:

1461680

Hom.:

173

Cov.:

AF XY:

0.0135

AC XY:

9830

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

33476

American (AMR)

AF:

0.00653

AC:

292

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00436

AC:

114

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00966

AC:

833

AN:

86220

European-Finnish (FIN)

AF:

0.0125

AC:

668

AN:

53410

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0156

AC:

17299

AN:

1111902

Other (OTH)

AF:

0.0105

AC:

633

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

964

1928

2893

3857

4821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.0112

AC:

1699

AN:

152310

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

798

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00274

AC:

114

AN:

41570

American (AMR)

AF:

0.00902

AC:

138

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00725

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0116

AC:

123

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0187

AC:

1269

AN:

68024

Other (OTH)

AF:

0.00614

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

171

256

342

427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00508

Hom.:

Bravo

AF:

0.00973

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0164

EpiControl

AF:

0.0141

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MMP1: BS1, BS2; WTAPP1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.5

Mutation Taster

=124/76

disease causing (fs/PTC)

(source)

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over