20-46008772-CCACACACACACACACACACACACACACACACACA-CCACACACACACACACACACACACACACACACA

Variant names:

• chr20-46008772-CCA-C
• rs2234681
• NM_004994.3:c.-154_-153delCA

Variant summary

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

The NM_004994.3(MMP9):​c.-154_-153delCA variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 978,204 control chromosomes in the GnomAD database, including 1,522 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1269 hom., cov: 0)
  • Exomes 𝑓: 0.077 (253 hom.)
• Consequence: MMP9 NM_004994.3 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00500

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-CCA-C is Benign according to our data. Variant chr20-46008772-CCA-C is described in ClinVar as [Benign]. Clinvar id is 1266514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP9	NM_004994.3	c.-154_-153delCA		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_-153delCA		upstream_gene_variant		1	NM_004994.3	ENSP00000361405.3

Frequencies

GnomAD3 genomes AF: 0.135 AC: 18959 AN: 140954 Hom.: 1268 Cov.: 0

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0942

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.0768 AC: 64312 AN: 837152 Hom.: 253 AF XY: 0.0796 AC XY: 33913 AN XY: 425812

Gnomad4 AFR exome AF: 0.0918

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.0638

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0648

Gnomad4 OTH exome AF: 0.0817

GnomAD4 genome AF: 0.135 AC: 18981 AN: 141052 Hom.: 1269 Cov.: 0 AF XY: 0.135 AC XY: 9203 AN XY: 68006

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.134

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 03, 2020

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;