Genetic Variant MMP7:c.484+659T>C (chr11-102526865-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002423.5(MMP7):c.484+659T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,394 control chromosomes in the GnomAD database, including 2,520 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2519 hom., cov: 31)

Exomes 𝑓: 0.15 ( 1 hom. )

Consequence

MMP7
NM_002423.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.323

Publications

11 publications found

Variant links:

Genes affected

MMP7 (HGNC:7174): (matrix metallopeptidase 7) 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 proteoglycans, fibronectin, elastin and casein and differs from most MMP family members in that it lacks a conserved C-terminal hemopexin domain. The enzyme is involved in wound healing, and studies in mice suggest that it regulates the activity of defensins in intestinal mucosa. The gene is part of a cluster of MMP genes on chromosome 11. This gene exhibits elevated expression levels in multiple human cancers. [provided by RefSeq, Jan 2016]

MMP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP7	NM_002423.5 link	c.484+659T>C		intron_variant	Intron 3 of 5	ENST00000260227.5	NP_002414.1	P09237

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMP7	ENST00000260227.5 link	c.484+659T>C	intron_variant	Intron 3 of 5	1	NM_002423.5	ENSP00000260227.4	P09237
MMP7	ENST00000533366.5 link	n.534+659T>C	intron_variant	Intron 3 of 3	2
MMP7	ENST00000531200.1 link	n.*121T>C	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24993

AN:

152052

Hom.:

2518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0412

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.0922

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.179

GnomAD4 exome

AF:

0.152

AC:

AN:

224

Hom.:

AF XY:

0.118

AC XY:

AN XY:

144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0556

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.163

AC:

AN:

190

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.164

AC:

24998

AN:

152170

Hom.:

2519

Cov.:

AF XY:

0.161

AC XY:

11998

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0410

AC:

1704

AN:

41528

American (AMR)

AF:

0.164

AC:

2501

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

787

AN:

3464

East Asian (EAS)

AF:

0.233

AC:

1208

AN:

5180

South Asian (SAS)

AF:

0.0929

AC:

448

AN:

4822

European-Finnish (FIN)

AF:

0.212

AC:

2247

AN:

10590

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15522

AN:

67980

Other (OTH)

AF:

0.178

AC:

375

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1024

2048

3073

4097

5121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<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:

0.193

Hom.:

519

Bravo

AF:

0.156

Asia WGS

AF:

0.133

AC:

462

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.2

(source)

DANN

Benign

0.35

PhyloP100

-0.32

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over