11-102795242-C-T

Variant names:

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.831G>A(p.Ala277Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,613,932 control chromosomes in the GnomAD database, including 715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 49 hom., cov: 33)

Exomes 𝑓: 0.028 ( 666 hom. )

Consequence

MMP1
NM_002421.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.24

Publications

8 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=-0.58).

BP6

Variant 11-102795242-C-T is Benign according to our data. Variant chr11-102795242-C-T is described in ClinVar as Benign. ClinVar VariationId is 403091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.24 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4 link	c.831G>A	p.Ala277Ala	synonymous_variant	Exon 6 of 10	ENST00000315274.7	NP_002412.1	P03956Q53G95
MMP1	NM_001145938.2 link	c.633G>A	p.Ala211Ala	synonymous_variant	Exon 6 of 10		NP_001139410.1	B4DN15
WTAPP1	NR_038390.1 link	n.583+18C>T		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7 link	c.831G>A	p.Ala277Ala	synonymous_variant	Exon 6 of 10	1	NM_002421.4	ENSP00000322788.6		P03956

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3162

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00734

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.0528

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.00774

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0301

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.0209

AC:

5230

AN:

250400

AF XY:

0.0221

show subpopulations

Gnomad AFR exome

AF:

0.00771

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.0572

Gnomad EAS exome

AF:

0.000707

Gnomad FIN exome

AF:

0.00582

Gnomad NFE exome

AF:

0.0294

Gnomad OTH exome

AF:

0.0306

GnomAD4 exome

AF:

0.0277

AC:

40535

AN:

1461668

Hom.:

666

Cov.:

AF XY:

0.0278

AC XY:

20204

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.00783

AC:

262

AN:

33476

American (AMR)

AF:

0.0173

AC:

772

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0575

AC:

1503

AN:

26130

East Asian (EAS)

AF:

0.000353

AC:

AN:

39696

South Asian (SAS)

AF:

0.0111

AC:

960

AN:

86256

European-Finnish (FIN)

AF:

0.00719

AC:

384

AN:

53382

Middle Eastern (MID)

AF:

0.0640

AC:

369

AN:

5762

European-Non Finnish (NFE)

AF:

0.0311

AC:

34581

AN:

1111874

Other (OTH)

AF:

0.0280

AC:

1690

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

2034

4068

6101

8135

10169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1320

2640

3960

5280

6600

<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:

0.0208

AC:

3163

AN:

152264

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

1471

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00736

AC:

306

AN:

41554

American (AMR)

AF:

0.0245

AC:

374

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0528

AC:

183

AN:

3468

East Asian (EAS)

AF:

0.000964

AC:

AN:

5188

South Asian (SAS)

AF:

0.0118

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00774

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0301

AC:

2047

AN:

68028

Other (OTH)

AF:

0.0255

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

161

322

482

643

804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0274

Hom.:

106

Bravo

AF:

0.0210

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0324

EpiControl

AF:

0.0343

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent variant not in splice consensus -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.1

(source)

DANN

Benign

0.61

PhyloP100

-1.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over