chr11-102724761-G-A

Variant names:

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.95C>T(p.Thr32Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,586,530 control chromosomes in the GnomAD database, including 261,255 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 0.63 ( 30389 hom., cov: 33)

Exomes 𝑓: 0.56 ( 230866 hom. )

Consequence

MMP8
NM_002424.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.684

Publications

50 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=4.8309057E-6).

BP6

Variant 11-102724761-G-A is Benign according to our data. Variant chr11-102724761-G-A is described in ClinVar as Benign. ClinVar VariationId is 403100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP8	NM_002424.3 link	c.95C>T	p.Thr32Ile	missense_variant	Exon 1 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.95C>T	p.Thr32Ile	missense_variant	Exon 1 of 10	1	NM_002424.3	ENSP00000236826.3		P22894

Frequencies

GnomAD3 genomes

AF:

0.626

AC:

95189

AN:

151996

Hom.:

30368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.756

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.587

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.610

Gnomad MID

AF:

0.742

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.635

GnomAD2 exomes

AF:

0.592

AC:

144728

AN:

244278

AF XY:

0.591

show subpopulations

Gnomad AFR exome

AF:

0.761

Gnomad AMR exome

AF:

0.551

Gnomad ASJ exome

AF:

0.613

Gnomad EAS exome

AF:

0.636

Gnomad FIN exome

AF:

0.598

Gnomad NFE exome

AF:

0.565

Gnomad OTH exome

AF:

0.605

GnomAD4 exome

AF:

0.564

AC:

809126

AN:

1434416

Hom.:

230866

Cov.:

AF XY:

0.565

AC XY:

402936

AN XY:

712980

show subpopulations

African (AFR)

AF:

0.765

AC:

25187

AN:

32918

American (AMR)

AF:

0.553

AC:

23828

AN:

43124

Ashkenazi Jewish (ASJ)

AF:

0.619

AC:

15844

AN:

25578

East Asian (EAS)

AF:

0.680

AC:

26618

AN:

39148

South Asian (SAS)

AF:

0.611

AC:

49741

AN:

81358

European-Finnish (FIN)

AF:

0.591

AC:

31151

AN:

52686

Middle Eastern (MID)

AF:

0.699

AC:

3965

AN:

5670

European-Non Finnish (NFE)

AF:

0.546

AC:

598127

AN:

1094788

Other (OTH)

AF:

0.586

AC:

34665

AN:

59146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

15550

31099

46649

62198

77748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17060

34120

51180

68240

85300

<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:

0.626

AC:

95245

AN:

152114

Hom.:

30389

Cov.:

AF XY:

0.628

AC XY:

46710

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.756

AC:

31378

AN:

41500

American (AMR)

AF:

0.586

AC:

8957

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

2104

AN:

3464

East Asian (EAS)

AF:

0.634

AC:

3282

AN:

5176

South Asian (SAS)

AF:

0.629

AC:

3036

AN:

4828

European-Finnish (FIN)

AF:

0.610

AC:

6446

AN:

10570

Middle Eastern (MID)

AF:

0.740

AC:

216

AN:

292

European-Non Finnish (NFE)

AF:

0.558

AC:

37942

AN:

67976

Other (OTH)

AF:

0.636

AC:

1345

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1818

3636

5454

7272

9090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.582

Hom.:

119175

Bravo

AF:

0.629

TwinsUK

AF:

0.529

AC:

1961

ALSPAC

AF:

0.554

AC:

2136

ESP6500AA

AF:

0.751

AC:

3309

ESP6500EA

AF:

0.557

AC:

4788

ExAC

AF:

0.597

AC:

72457

Asia WGS

AF:

0.662

AC:

2299

AN:

3478

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

0.062

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.61

CADD

Benign

4.0

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.028

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00022

LIST_S2

Benign

0.0083

MetaRNN

Benign

0.0000048

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.1

PhyloP100

0.68

PrimateAI

Benign

0.36

PROVEAN

Benign

2.3

REVEL

Benign

0.052

Sift

Benign

0.27

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.022

MPC

0.041

ClinPred

0.0031

GERP RS

0.96

PromoterAI

-0.027

Neutral

(source)

Varity_R

0.037

gMVP

0.18

Mutation Taster

=99/1

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