dbSNP rs470558: MMP1:p.Ala216Ala (chr11-102795585-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002421.4(MMP1):c.648A>G(p.Ala216Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 1,612,654 control chromosomes in the GnomAD database, including 715,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68631 hom., cov: 31)

Exomes 𝑓: 0.94 ( 646820 hom. )

Consequence

MMP1
NM_002421.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.36

Publications

39 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-102795585-T-C is Benign according to our data. Variant chr11-102795585-T-C is described in ClinVar as Benign. ClinVar VariationId is 403092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.98 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	HGVSp	Effect	Exon Rank	Protein	UniProt
MMP1	NM_002421.4	MANE Select	c.648A>G	p.Ala216Ala	synonymous	Exon 5 of 10	NP_002412.1	P03956
MMP1	NM_001145938.2		c.450A>G	p.Ala150Ala	synonymous	Exon 5 of 10	NP_001139410.1	B4DN15
WTAPP1	NR_038390.1		n.583+361T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMP1	ENST00000315274.7	TSL:1 MANE Select	c.648A>G	p.Ala216Ala	synonymous	Exon 5 of 10	ENSP00000322788.6	P03956
WTAPP1	ENST00000371455.7	TSL:4	n.325-2439T>C		intron	N/A
WTAPP1	ENST00000525739.6	TSL:2	n.583+361T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.949

AC:

144315

AN:

152090

Hom.:

68573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.988

Gnomad AMI

AF:

0.932

Gnomad AMR

AF:

0.903

Gnomad ASJ

AF:

0.921

Gnomad EAS

AF:

0.894

Gnomad SAS

AF:

0.904

Gnomad FIN

AF:

0.917

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.949

Gnomad OTH

AF:

0.939

GnomAD2 exomes

AF:

0.924

AC:

230883

AN:

249836

AF XY:

0.926

show subpopulations

Gnomad AFR exome

AF:

0.989

Gnomad AMR exome

AF:

0.845

Gnomad ASJ exome

AF:

0.928

Gnomad EAS exome

AF:

0.886

Gnomad FIN exome

AF:

0.922

Gnomad NFE exome

AF:

0.952

Gnomad OTH exome

AF:

0.934

GnomAD4 exome

AF:

0.941

AC:

1373872

AN:

1460448

Hom.:

646820

Cov.:

AF XY:

0.940

AC XY:

682628

AN XY:

726446

show subpopulations

African (AFR)

AF:

0.991

AC:

33138

AN:

33424

American (AMR)

AF:

0.852

AC:

37783

AN:

44352

Ashkenazi Jewish (ASJ)

AF:

0.929

AC:

24252

AN:

26102

East Asian (EAS)

AF:

0.884

AC:

35096

AN:

39686

South Asian (SAS)

AF:

0.898

AC:

77098

AN:

85860

European-Finnish (FIN)

AF:

0.927

AC:

49496

AN:

53370

Middle Eastern (MID)

AF:

0.936

AC:

5388

AN:

5758

European-Non Finnish (NFE)

AF:

0.949

AC:

1054967

AN:

1111538

Other (OTH)

AF:

0.939

AC:

56654

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3786

7572

11358

15144

18930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21588

43176

64764

86352

107940

<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:

0.949

AC:

144431

AN:

152206

Hom.:

68631

Cov.:

AF XY:

0.945

AC XY:

70339

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.988

AC:

41044

AN:

41522

American (AMR)

AF:

0.903

AC:

13814

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.921

AC:

3197

AN:

3470

East Asian (EAS)

AF:

0.894

AC:

4631

AN:

5178

South Asian (SAS)

AF:

0.903

AC:

4351

AN:

4818

European-Finnish (FIN)

AF:

0.917

AC:

9706

AN:

10588

Middle Eastern (MID)

AF:

0.929

AC:

273

AN:

294

European-Non Finnish (NFE)

AF:

0.949

AC:

64584

AN:

68024

Other (OTH)

AF:

0.940

AC:

1981

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

377

754

1130

1507

1884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.945

Hom.:

102578

Bravo

AF:

0.948

Asia WGS

AF:

0.912

AC:

3173

AN:

3478

EpiCase

AF:

0.947

EpiControl

AF:

0.946

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.18

(source)

DANN

Benign

0.49

PhyloP100

-3.4

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