dbSNP rs17884110: MMP1:c.900-8dupC (chr11-102792745-A-AG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_002421.4(MMP1):c.900-8dupC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,605,804 control chromosomes in the GnomAD database, including 94,809 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 7294 hom., cov: 0)

Exomes 𝑓: 0.34 ( 87515 hom. )

Consequence

MMP1
NM_002421.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.776

Publications

5 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 11-102792745-A-AG is Benign according to our data. Variant chr11-102792745-A-AG is described in ClinVar as Benign. ClinVar VariationId is 403089.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002421.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MMP1	NM_002421.4	MANE Select	c.900-8dupC	splice_region intron	N/A	NP_002412.1	P03956
MMP1	NM_001145938.2		c.702-8dupC	splice_region intron	N/A	NP_001139410.1	B4DN15
WTAPP1	NR_038390.1		n.390-399dupG	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MMP1	ENST00000315274.7	TSL:1 MANE Select	c.900-8dupC	splice_region intron	N/A	ENSP00000322788.6	P03956
MMP1	ENST00000681643.1		n.92dupC	non_coding_transcript_exon	Exon 1 of 4
WTAPP1	ENST00000371455.7	TSL:4	n.325-5278dupG	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45532

AN:

151848

Hom.:

7297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.0843

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.293

GnomAD2 exomes

AF:

0.302

AC:

74610

AN:

247314

AF XY:

0.309

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.0813

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.361

Gnomad OTH exome

AF:

0.321

GnomAD4 exome

AF:

0.342

AC:

497503

AN:

1453838

Hom.:

87515

Cov.:

AF XY:

0.343

AC XY:

247747

AN XY:

722882

show subpopulations

African (AFR)

AF:

0.233

AC:

7751

AN:

33252

American (AMR)

AF:

0.210

AC:

9247

AN:

44076

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

10348

AN:

25986

East Asian (EAS)

AF:

0.115

AC:

4565

AN:

39632

South Asian (SAS)

AF:

0.318

AC:

27004

AN:

84806

European-Finnish (FIN)

AF:

0.310

AC:

16524

AN:

53362

Middle Eastern (MID)

AF:

0.320

AC:

1836

AN:

5742

European-Non Finnish (NFE)

AF:

0.362

AC:

400537

AN:

1106864

Other (OTH)

AF:

0.328

AC:

19691

AN:

60118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

13476

26951

40427

53902

67378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12522

25044

37566

50088

62610

<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:

0.300

AC:

45533

AN:

151966

Hom.:

7294

Cov.:

AF XY:

0.293

AC XY:

21794

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.236

AC:

9791

AN:

41478

American (AMR)

AF:

0.242

AC:

3702

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

1390

AN:

3464

East Asian (EAS)

AF:

0.0839

AC:

435

AN:

5186

South Asian (SAS)

AF:

0.321

AC:

1540

AN:

4804

European-Finnish (FIN)

AF:

0.287

AC:

3032

AN:

10558

Middle Eastern (MID)

AF:

0.274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.364

AC:

24698

AN:

67898

Other (OTH)

AF:

0.290

AC:

612

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1642

3284

4926

6568

8210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.337

Hom.:

1837

Bravo

AF:

0.289

Asia WGS

AF:

0.224

AC:

777

AN:

3478

EpiCase

AF:

0.368

EpiControl

AF:

0.355

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.78

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