rs35231465

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_002424.3(MMP8):c.1348C>T(p.Gln450*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 1,613,238 control chromosomes in the GnomAD database, including 442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 38 hom., cov: 33)

Exomes 𝑓: 0.021 ( 404 hom. )

Consequence

MMP8
NM_002424.3 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.07

Publications

24 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 -16 ACMG points.

BP6

Variant 11-102713404-G-A is Benign according to our data. Variant chr11-102713404-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 403101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0154 (2340/152260) while in subpopulation NFE AF = 0.0244 (1662/68010). AF 95% confidence interval is 0.0235. There are 38 homozygotes in GnomAd4. There are 1075 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 38 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP8	NM_002424.3 link	c.1348C>T	p.Gln450*	stop_gained	Exon 10 of 10	ENST00000236826.8	NP_002415.1	P22894

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMP8	ENST00000236826.8 link	c.1348C>T	p.Gln450*	stop_gained	Exon 10 of 10	1	NM_002424.3	ENSP00000236826.3	P22894
MMP8	ENST00000528662.6 link	n.*1325C>T		non_coding_transcript_exon_variant	Exon 12 of 12	5		ENSP00000431431.2	E9PL87
MMP8	ENST00000438475.2 link	c.*87C>T		3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000401004.2	H7C1M3
MMP8	ENST00000528662.6 link	n.*1325C>T		3_prime_UTR_variant	Exon 12 of 12	5		ENSP00000431431.2	E9PL87

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2340

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00490

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0244

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.0163

AC:

4086

AN:

250812

AF XY:

0.0165

show subpopulations

Gnomad AFR exome

AF:

0.00394

Gnomad AMR exome

AF:

0.0122

Gnomad ASJ exome

AF:

0.0196

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0163

Gnomad NFE exome

AF:

0.0256

Gnomad OTH exome

AF:

0.0200

GnomAD4 exome

AF:

0.0212

AC:

30974

AN:

1460978

Hom.:

404

Cov.:

AF XY:

0.0207

AC XY:

15051

AN XY:

726828

show subpopulations

African (AFR)

AF:

0.00275

AC:

AN:

33444

American (AMR)

AF:

0.0127

AC:

569

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

519

AN:

26120

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39666

South Asian (SAS)

AF:

0.00129

AC:

111

AN:

86242

European-Finnish (FIN)

AF:

0.0174

AC:

927

AN:

53400

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0248

AC:

27580

AN:

1111280

Other (OTH)

AF:

0.0185

AC:

1116

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

1428

2856

4284

5712

7140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

998

1996

2994

3992

4990

<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:

0.0154

AC:

2340

AN:

152260

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1075

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00488

AC:

203

AN:

41564

American (AMR)

AF:

0.0146

AC:

223

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00104

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0130

AC:

138

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0244

AC:

1662

AN:

68010

Other (OTH)

AF:

0.0170

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

121

242

362

483

604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0220

Hom.:

150

Bravo

AF:

0.0156

TwinsUK

AF:

0.0259

AC:

ALSPAC

AF:

0.0304

AC:

117

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.0226

AC:

194

ExAC

AF:

0.0161

AC:

1950

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0251

EpiControl

AF:

0.0254

ClinVar

Significance: Likely 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:Likely 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 in ESP (all): 214/13004= 1.64% -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Benign

0.73

Eigen

Benign

-0.84

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.095

PhyloP100

2.1

Vest4

0.67

GERP RS

-2.5

Mutation Taster

=165/35

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