20-46008772-CCACACACACACACACACACACACACACACACACA-CCACACACACACACACA

Variant names:

• chr20-46008772-CCACACACACACACACACA-C
• rs2234681
• NM_004994.3:c.-154_-137delCACACACACACACACACA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004994.3(MMP9):​c.-154_-137delCACACACACACACACACA variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 995,748 control chromosomes in the GnomAD database, including 69,970 homozygotes. 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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14540 hom., cov: 0)
  • Exomes 𝑓: 0.43 (55430 hom.)
• Consequence: MMP9 NM_004994.3 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.65
• Publications: 21 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 20-46008772-CCACACACACACACACACA-C is Benign according to our data. Variant chr20-46008772-CCACACACACACACACACA-C is described in ClinVar as Benign. ClinVar VariationId is 1272639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004994.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP9	NM_004994.3	MANE Select	c.-154_-137delCACACACACACACACACA		upstream_gene	N/A	NP_004985.2	P14780

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP9	ENST00000372330.3	TSL:1 MANE Select	c.-154_-137delCACACACACACACACACA		upstream_gene	N/A	ENSP00000361405.3	P14780
	MMP9	ENST00000898203.1		c.-154_-137delCACACACACACACACACA		upstream_gene	N/A	ENSP00000568262.1
	MMP9	ENST00000898204.1		c.-154_-137delCACACACACACACACACA		upstream_gene	N/A	ENSP00000568263.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 61116 AN: 141518 Hom.: 14547 Cov.: 0

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.00505

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.435 AC: 371442 AN: 854128 Hom.: 55430 AF XY: 0.428 AC XY: 186102 AN XY: 434984

African (AFR) AF: 0.238 AC: 4498 AN: 18920

American (AMR) AF: 0.231 AC: 7307 AN: 31606

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 8006 AN: 19518

East Asian (EAS) AF: 0.00146 AC: 41 AN: 28172

South Asian (SAS) AF: 0.280 AC: 17752 AN: 63430

European-Finnish (FIN) AF: 0.392 AC: 12291 AN: 31388

Middle Eastern (MID) AF: 0.434 AC: 1285 AN: 2960

European-Non Finnish (NFE) AF: 0.491 AC: 304519 AN: 619600

Other (OTH) AF: 0.409 AC: 15743 AN: 38534

GnomAD4 genome AF: 0.432 AC: 61114 AN: 141620 Hom.: 14540 Cov.: 0 AF XY: 0.424 AC XY: 28940 AN XY: 68286

African (AFR) AF: 0.261 AC: 9722 AN: 37186

American (AMR) AF: 0.368 AC: 5246 AN: 14270

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1703 AN: 3396

East Asian (EAS) AF: 0.00483 AC: 21 AN: 4344

South Asian (SAS) AF: 0.317 AC: 1325 AN: 4184

European-Finnish (FIN) AF: 0.497 AC: 4591 AN: 9232

Middle Eastern (MID) AF: 0.566 AC: 162 AN: 286

European-Non Finnish (NFE) AF: 0.561 AC: 36949 AN: 65898

Other (OTH) AF: 0.460 AC: 886 AN: 1926

Alfa AF: 0.464 Hom.: 555

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs2234681; hg19: chr20-44637411;