NM_004994.3:c.-154_-153delCA

Variant names:

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

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_-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
• 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-CCA-C is Benign according to our data. Variant chr20-46008772-CCA-C is described in ClinVar as Benign. ClinVar VariationId 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.

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_-153delCA		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_-153delCA		upstream_gene	N/A	ENSP00000361405.3	P14780
	MMP9	ENST00000898203.1		c.-154_-153delCA		upstream_gene	N/A	ENSP00000568262.1
	MMP9	ENST00000898204.1		c.-154_-153delCA		upstream_gene	N/A	ENSP00000568263.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0918 AC: 1707 AN: 18594

American (AMR) AF: 0.128 AC: 3943 AN: 30914

Ashkenazi Jewish (ASJ) AF: 0.0638 AC: 1224 AN: 19176

East Asian (EAS) AF: 0.123 AC: 3410 AN: 27780

South Asian (SAS) AF: 0.130 AC: 7956 AN: 61022

European-Finnish (FIN) AF: 0.111 AC: 3378 AN: 30502

Middle Eastern (MID) AF: 0.0676 AC: 197 AN: 2916

European-Non Finnish (NFE) AF: 0.0648 AC: 39421 AN: 608598

Other (OTH) AF: 0.0817 AC: 3076 AN: 37650

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.135 AC: 4993 AN: 37032

American (AMR) AF: 0.130 AC: 1856 AN: 14236

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 349 AN: 3386

East Asian (EAS) AF: 0.119 AC: 518 AN: 4340

South Asian (SAS) AF: 0.170 AC: 707 AN: 4168

European-Finnish (FIN) AF: 0.161 AC: 1476 AN: 9144

Middle Eastern (MID) AF: 0.0880 AC: 25 AN: 284

European-Non Finnish (NFE) AF: 0.132 AC: 8685 AN: 65648

Other (OTH) AF: 0.134 AC: 257 AN: 1920

Alfa AF: 0.121 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		-0.0050

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;