20-46008772-CCACACACACACACACACACACACACACACACACA-CCACACACACACACACACACACACA

Variant names:

• chr20-46008772-CCACACACACA-C
• rs2234681
• NM_004994.3:c.-154_-145delCACACACACA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_004994.3(MMP9):​c.-154_-145delCACACACACA variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 995,694 control chromosomes in the GnomAD database, including 37 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0095 (28 hom., cov: 0)
  • Exomes 𝑓: 0.0032 (9 hom.)
• Consequence: MMP9 NM_004994.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00953 (1349/141622) while in subpopulation AFR AF= 0.033 (1227/37184). AF 95% confidence interval is 0.0315. There are 28 homozygotes in gnomad4. There are 640 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP9	NM_004994.3	c.-154_-145delCACACACACA		upstream_gene_variant		ENST00000372330.3	NP_004985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3	c.-154_-145delCACACACACA		upstream_gene_variant		1	NM_004994.3	ENSP00000361405.3

Frequencies

GnomAD3 genomes AF: 0.00949 AC: 1343 AN: 141520 Hom.: 28 Cov.: 0

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.000589

Gnomad EAS AF: 0.000459

Gnomad SAS AF: 0.00453

Gnomad FIN AF: 0.000108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000622

Gnomad OTH AF: 0.00838

GnomAD4 exome AF: 0.00321 AC: 2738 AN: 854072 Hom.: 9 AF XY: 0.00336 AC XY: 1461 AN XY: 434966

Gnomad4 AFR exome AF: 0.0329

Gnomad4 AMR exome AF: 0.00354

Gnomad4 ASJ exome AF: 0.00323

Gnomad4 EAS exome AF: 0.00467

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.00264

Gnomad4 NFE exome AF: 0.00142

Gnomad4 OTH exome AF: 0.00498

GnomAD4 genome AF: 0.00953 AC: 1349 AN: 141622 Hom.: 28 Cov.: 0 AF XY: 0.00937 AC XY: 640 AN XY: 68284

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.00287

Gnomad4 ASJ AF: 0.000589

Gnomad4 EAS AF: 0.000460

Gnomad4 SAS AF: 0.00454

Gnomad4 FIN AF: 0.000108

Gnomad4 NFE AF: 0.000622

Gnomad4 OTH AF: 0.00830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2234681; hg19: chr20-44637411;