20-46008772-CCACACACACACACACACACACACACACACACACA-CCACACACACACACACA

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP9	NM_004994.3	c.-154_-137delCACACACACACACACACA		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_-137delCACACACACACACACACA		upstream_gene_variant		1	NM_004994.3	ENSP00000361405.3

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

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.00146

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.491

Gnomad4 OTH exome AF: 0.409

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

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.00483

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 23, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;