20-46008772-CCACACACACACACACACACACACACACACACACA-CCACACACACACACACACACACACACACA

Variant names:

• chr20-46008772-CCACACA-C
• rs2234681
• NM_004994.3:c.-154_-149delCACACA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004994.3(MMP9):​c.-154_-149delCACACA variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 988,898 control chromosomes in the GnomAD database, including 350 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (266 hom., cov: 0)
  • Exomes 𝑓: 0.037 (84 hom.)
• Consequence: MMP9 NM_004994.3 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.281

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-CCACACA-C is Benign according to our data. Variant chr20-46008772-CCACACA-C is described in ClinVar as [Benign]. Clinvar id is 1261573.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP9	NM_004994.3	c.-154_-149delCACACA		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_-149delCACACA		upstream_gene_variant		1	NM_004994.3	ENSP00000361405.3

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6046 AN: 141400 Hom.: 265 Cov.: 0

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0167

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.00914

Gnomad EAS AF: 0.0315

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.0290

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0320

GnomAD4 exome AF: 0.0372 AC: 31538 AN: 847396 Hom.: 84 AF XY: 0.0380 AC XY: 16398 AN XY: 431520

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0618

Gnomad4 ASJ exome AF: 0.0383

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.0529

Gnomad4 FIN exome AF: 0.0496

Gnomad4 NFE exome AF: 0.0255

Gnomad4 OTH exome AF: 0.0437

GnomAD4 genome AF: 0.0428 AC: 6054 AN: 141502 Hom.: 266 Cov.: 0 AF XY: 0.0431 AC XY: 2937 AN XY: 68222

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.00914

Gnomad4 EAS AF: 0.0313

Gnomad4 SAS AF: 0.0399

Gnomad4 FIN AF: 0.0244

Gnomad4 NFE AF: 0.0163

Gnomad4 OTH AF: 0.0322

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 02, 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;