Genetic Variant MMP9:c.-154_-133delCACACACACACACACACACACA (chr20-46008772-CCACACACACACACACACACACA-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004994.3(MMP9):c.-154_-133delCACACACACACACACACACACA variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 990,842 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0013 ( 4 hom. )

Consequence

MMP9
NM_004994.3 upstream_gene

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.65

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP9	NM_004994.3 link	c.-154_-133delCACACACACACACACACACACA		upstream_gene_variant		ENST00000372330.3	NP_004985.2	P14780

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3 link	c.-154_-133delCACACACACACACACACACACA		upstream_gene_variant		1	NM_004994.3	ENSP00000361405.3		P14780

Frequencies

GnomAD3 genomes

AF:

0.0000989

AC:

AN:

141532

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000702

Gnomad ASJ

AF:

0.000589

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00131

AC:

1113

AN:

849208

Hom.:

AF XY:

0.00134

AC XY:

581

AN XY:

432482

show subpopulations

Gnomad4 AFR exome

AF:

0.000846

Gnomad4 AMR exome

AF:

0.000475

Gnomad4 ASJ exome

AF:

0.00165

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000426

Gnomad4 FIN exome

AF:

0.00106

Gnomad4 NFE exome

AF:

0.00150

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.0000988

AC:

AN:

141634

Hom.:

Cov.:

AF XY:

0.0000732

AC XY:

AN XY:

68292

show subpopulations

Gnomad4 AFR

AF:

0.0000269

Gnomad4 AMR

AF:

0.0000701

Gnomad4 ASJ

AF:

0.000589

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000152

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

20-46008772-CCACACACACACACACACACACACACACACACACA-CCACACACACACA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over