rs1940475

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002424.3(MMP8):c.259A>G(p.Lys87Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,613,576 control chromosomes in the GnomAD database, including 220,484 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24270 hom., cov: 31)

Exomes 𝑓: 0.52 ( 196214 hom. )

Consequence

MMP8
NM_002424.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.167

Publications

79 publications found

Variant links:

Genes affected

MMP8 (HGNC:7175): (matrix metallopeptidase 8) This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

MMP8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.5295376E-6).

BP6

Variant 11-102722517-T-C is Benign according to our data. Variant chr11-102722517-T-C is described in ClinVar as Benign. ClinVar VariationId is 403099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP8	NM_002424.3 link	c.259A>G	p.Lys87Glu	missense_variant	Exon 2 of 10	ENST00000236826.8	NP_002415.1	P22894

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826.8 link	c.259A>G	p.Lys87Glu	missense_variant	Exon 2 of 10	1	NM_002424.3	ENSP00000236826.3		P22894

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

85350

AN:

151852

Hom.:

24262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.648

Gnomad AMI

AF:

0.557

Gnomad AMR

AF:

0.543

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.627

Gnomad SAS

AF:

0.575

Gnomad FIN

AF:

0.558

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.509

Gnomad OTH

AF:

0.571

GnomAD2 exomes

AF:

0.541

AC:

136053

AN:

251338

AF XY:

0.539

show subpopulations

Gnomad AFR exome

AF:

0.655

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.549

Gnomad EAS exome

AF:

0.631

Gnomad FIN exome

AF:

0.547

Gnomad NFE exome

AF:

0.513

Gnomad OTH exome

AF:

0.540

GnomAD4 exome

AF:

0.516

AC:

753941

AN:

1461606

Hom.:

196214

Cov.:

AF XY:

0.517

AC XY:

375684

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.653

AC:

21866

AN:

33460

American (AMR)

AF:

0.519

AC:

23215

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.556

AC:

14535

AN:

26126

East Asian (EAS)

AF:

0.675

AC:

26790

AN:

39694

South Asian (SAS)

AF:

0.554

AC:

47786

AN:

86256

European-Finnish (FIN)

AF:

0.540

AC:

28831

AN:

53416

Middle Eastern (MID)

AF:

0.604

AC:

3485

AN:

5768

European-Non Finnish (NFE)

AF:

0.499

AC:

555173

AN:

1111798

Other (OTH)

AF:

0.534

AC:

32260

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

22900

45801

68701

91602

114502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16262

32524

48786

65048

81310

<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:

0.562

AC:

85387

AN:

151970

Hom.:

24270

Cov.:

AF XY:

0.564

AC XY:

41880

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.648

AC:

26851

AN:

41468

American (AMR)

AF:

0.542

AC:

8269

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.547

AC:

1898

AN:

3468

East Asian (EAS)

AF:

0.628

AC:

3247

AN:

5172

South Asian (SAS)

AF:

0.572

AC:

2757

AN:

4816

European-Finnish (FIN)

AF:

0.558

AC:

5878

AN:

10536

Middle Eastern (MID)

AF:

0.629

AC:

185

AN:

294

European-Non Finnish (NFE)

AF:

0.509

AC:

34587

AN:

67938

Other (OTH)

AF:

0.573

AC:

1208

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1941

3883

5824

7766

9707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.528

Hom.:

71355

Bravo

AF:

0.563

TwinsUK

AF:

0.483

AC:

1791

ALSPAC

AF:

0.513

AC:

1977

ESP6500AA

AF:

0.647

AC:

2849

ESP6500EA

AF:

0.506

AC:

4348

ExAC

AF:

0.542

AC:

65814

Asia WGS

AF:

0.629

AC:

2185

AN:

3478

EpiCase

AF:

0.515

EpiControl

AF:

0.523

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: Frequency -

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

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.35

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.079

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0000025

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.4

PhyloP100

-0.17

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.4

REVEL

Benign

0.052

Sift

Benign

0.17

Sift4G

Benign

0.098

Polyphen

0.010

Vest4

0.020

MPC

0.049

ClinPred

0.0076

GERP RS

-6.1

Varity_R

0.065

gMVP

0.37

Mutation Taster

=86/14

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