Genetic Variant MMP9:c.-154_-125delCACACACACACACACACACACACACACACA (chr20-46008772-CCACACACACACACACACACACACACACACA-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_004994.3(MMP9):c.-154_-125delCACACACACACACACACACACACACACACA variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000819 in 854,856 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MMP9
NM_004994.3 upstream_gene

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.65

Publications

0 publications found

Variant links:

Genes affected

MMP9 (HGNC:7176): (matrix metallopeptidase 9) 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. The enzyme encoded by this gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling. [provided by RefSeq, Jul 2008]

MMP9 Gene-Disease associations (from GenCC):

metaphyseal anadysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
metaphyseal anadysplasia 2
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MMP9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BS2

High AC in GnomAdExome4 at 7 Unknown,AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP9	NM_004994.3 link	c.-154_-125delCACACACACACACACACACACACACACACA		upstream_gene_variant		ENST00000372330.3	NP_004985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3 link	c.-154_-125delCACACACACACACACACACACACACACACA		upstream_gene_variant		1	NM_004994.3	ENSP00000361405.3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

141536

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000819

AC:

AN:

854856

Hom.:

AF XY:

0.0000138

AC XY:

AN XY:

435410

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18950

American (AMR)

AF:

0.00

AC:

AN:

31658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19556

East Asian (EAS)

AF:

0.00

AC:

AN:

28172

South Asian (SAS)

AF:

0.00

AC:

AN:

63516

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31422

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2964

European-Non Finnish (NFE)

AF:

0.0000113

AC:

AN:

620056

Other (OTH)

AF:

0.00

AC:

AN:

38562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

141536

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68178

African (AFR)

AF:

0.00

AC:

AN:

37080

American (AMR)

AF:

0.00

AC:

AN:

14252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3394

East Asian (EAS)

AF:

0.00

AC:

AN:

4358

South Asian (SAS)

AF:

0.00

AC:

AN:

4190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65910

Other (OTH)

AF:

0.00

AC:

AN:

1910

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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20-46008772-CCACACACACACACACACACACACACACACACACA-CCACA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over