Genetic Variant NM_002423.5:c.230G>A (chr11-102527862-C-T) – 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.230G>A(p.Arg77His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,613,680 control chromosomes in the GnomAD database, including 37,027 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R77R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.16 ( 2529 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34498 hom. )

Consequence

MMP7
NM_002423.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.285

Publications

53 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0057508945).

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.230G>A	p.Arg77His	missense_variant	Exon 2 of 6	ENST00000260227.5	NP_002414.1	P09237

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMP7	ENST00000260227.5 link	c.230G>A	p.Arg77His	missense_variant	Exon 2 of 6	1	NM_002423.5	ENSP00000260227.4	P09237
MMP7	ENST00000531200.1 link	n.277G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2
MMP7	ENST00000533366.5 link	n.280G>A		non_coding_transcript_exon_variant	Exon 2 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24957

AN:

151944

Hom.:

2528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0401

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.0917

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.177

GnomAD2 exomes

AF:

0.188

AC:

47272

AN:

251434

AF XY:

0.187

show subpopulations

Gnomad AFR exome

AF:

0.0393

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.255

Gnomad FIN exome

AF:

0.229

Gnomad NFE exome

AF:

0.221

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.211

AC:

307798

AN:

1461618

Hom.:

34498

Cov.:

AF XY:

0.209

AC XY:

151721

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.0326

AC:

1092

AN:

33480

American (AMR)

AF:

0.157

AC:

6999

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

6150

AN:

26128

East Asian (EAS)

AF:

0.219

AC:

8698

AN:

39692

South Asian (SAS)

AF:

0.0970

AC:

8370

AN:

86258

European-Finnish (FIN)

AF:

0.236

AC:

12594

AN:

53406

Middle Eastern (MID)

AF:

0.145

AC:

838

AN:

5768

European-Non Finnish (NFE)

AF:

0.226

AC:

250961

AN:

1111772

Other (OTH)

AF:

0.200

AC:

12096

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

13571

27142

40713

54284

67855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8398

16796

25194

33592

41990

<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:

24962

AN:

152062

Hom.:

2529

Cov.:

AF XY:

0.161

AC XY:

11981

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0400

AC:

1662

AN:

41520

American (AMR)

AF:

0.164

AC:

2505

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

790

AN:

3470

East Asian (EAS)

AF:

0.233

AC:

1204

AN:

5178

South Asian (SAS)

AF:

0.0924

AC:

445

AN:

4814

European-Finnish (FIN)

AF:

0.214

AC:

2255

AN:

10554

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15526

AN:

67948

Other (OTH)

AF:

0.175

AC:

369

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1021

2041

3062

4082

5103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<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:

0.201

Hom.:

11409

Bravo

AF:

0.156

TwinsUK

AF:

0.230

AC:

851

ALSPAC

AF:

0.231

AC:

891

ESP6500AA

AF:

0.0461

AC:

203

ESP6500EA

AF:

0.219

AC:

1884

ExAC

AF:

0.185

AC:

22492

Asia WGS

AF:

0.132

AC:

460

AN:

3478

EpiCase

AF:

0.219

EpiControl

AF:

0.213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.027

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.049

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.094

MetaRNN

Benign

0.0058

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.74

PhyloP100

-0.28

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.24

REVEL

Benign

0.069

Sift

Benign

0.15

Sift4G

Benign

0.15

Polyphen

0.012

Vest4

0.029

MPC

0.031

ClinPred

0.0031

GERP RS

-7.8

Varity_R

0.051

gMVP

0.28

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

Computational scores

Splicing

Publications

Other links and lift over