dbSNP rs28363645: MMP11:c.109-86G>A (chr22-23779101-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005940.5(MMP11):c.109-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,092,624 control chromosomes in the GnomAD database, including 813 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 0.035 ( 140 hom., cov: 33)

Exomes 𝑓: 0.034 ( 673 hom. )

Consequence

MMP11
NM_005940.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.65

Publications

3 publications found

Variant links:

Genes affected

MMP11 (HGNC:7157): (matrix metallopeptidase 11) Proteins of the matrix metalloproteinase (MMP) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is activated intracellularly by furin within the constitutive secretory pathway. Also in contrast to other MMP's, this enzyme cleaves alpha 1-proteinase inhibitor but weakly degrades structural proteins of the extracellular matrix. [provided by RefSeq, Jul 2008]

MMP11 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 (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP11	NM_005940.5 link	c.109-86G>A		intron_variant	Intron 1 of 7	ENST00000215743.8	NP_005931.2	P24347B3KQS8
MMP11	NR_133013.2 link	n.131-86G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP11	ENST00000215743.8 link	c.109-86G>A		intron_variant	Intron 1 of 7	1	NM_005940.5	ENSP00000215743.3		P24347

Frequencies

GnomAD3 genomes

AF:

0.0346

AC:

5266

AN:

152188

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0340

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0207

Gnomad ASJ

AF:

0.0524

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.0457

Gnomad FIN

AF:

0.0220

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0319

Gnomad OTH

AF:

0.0455

GnomAD4 exome

AF:

0.0343

AC:

32207

AN:

940318

Hom.:

673

AF XY:

0.0346

AC XY:

16216

AN XY:

468512

show subpopulations

African (AFR)

AF:

0.0338

AC:

802

AN:

23746

American (AMR)

AF:

0.0180

AC:

526

AN:

29242

Ashkenazi Jewish (ASJ)

AF:

0.0481

AC:

918

AN:

19090

East Asian (EAS)

AF:

0.0874

AC:

2897

AN:

33136

South Asian (SAS)

AF:

0.0437

AC:

2708

AN:

62036

European-Finnish (FIN)

AF:

0.0247

AC:

780

AN:

31574

Middle Eastern (MID)

AF:

0.0916

AC:

431

AN:

4704

European-Non Finnish (NFE)

AF:

0.0308

AC:

21356

AN:

694038

Other (OTH)

AF:

0.0418

AC:

1789

AN:

42752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1636

3272

4909

6545

8181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0346

AC:

5272

AN:

152306

Hom.:

140

Cov.:

AF XY:

0.0351

AC XY:

2613

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0342

AC:

1420

AN:

41570

American (AMR)

AF:

0.0207

AC:

317

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0524

AC:

182

AN:

3472

East Asian (EAS)

AF:

0.115

AC:

596

AN:

5178

South Asian (SAS)

AF:

0.0466

AC:

225

AN:

4830

European-Finnish (FIN)

AF:

0.0220

AC:

234

AN:

10622

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0319

AC:

2171

AN:

68012

Other (OTH)

AF:

0.0445

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

263

526

789

1052

1315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0332

Hom.:

116

Bravo

AF:

0.0346

Asia WGS

AF:

0.0630

AC:

218

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.0050

(source)

DANN

Benign

0.36

PhyloP100

-2.7

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

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rs28363645

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