rs3918253

Variant names:

• chr20-46010872-C-T
• rs3918253
• NM_004994.3:c.521-50C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004994.3(MMP9):​c.521-50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 1,613,584 control chromosomes in the GnomAD database, including 229,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (16134 hom., cov: 34)
  • Exomes 𝑓: 0.52 (213825 hom.)
• Consequence: MMP9 NM_004994.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.194
• Publications: 44 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 20-46010872-C-T is Benign according to our data. Variant chr20-46010872-C-T is described in ClinVar as Benign. ClinVar VariationId is 1281057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 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.521-50C>T		intron	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.521-50C>T		intron	N/A	ENSP00000361405.3	P14780
	MMP9	ENST00000898203.1		c.521-50C>T		intron	N/A	ENSP00000568262.1
	MMP9	ENST00000898204.1		c.520+241C>T		intron	N/A	ENSP00000568263.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65615 AN: 152104 Hom.: 16139 Cov.: 34

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.471

GnomAD2 exomes AF: 0.425 AC: 105470 AN: 248058 AF XY: 0.436

Gnomad AFR exome AF: 0.248

Gnomad AMR exome AF: 0.257

Gnomad ASJ exome AF: 0.512

Gnomad EAS exome AF: 0.00223

Gnomad FIN exome AF: 0.479

Gnomad NFE exome AF: 0.578

Gnomad OTH exome AF: 0.488

GnomAD4 exome AF: 0.525 AC: 766661 AN: 1461362 Hom.: 213825 Cov.: 49 AF XY: 0.521 AC XY: 378831 AN XY: 726964

African (AFR) AF: 0.237 AC: 7947 AN: 33480

American (AMR) AF: 0.270 AC: 12084 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 13265 AN: 26134

East Asian (EAS) AF: 0.00139 AC: 55 AN: 39688

South Asian (SAS) AF: 0.334 AC: 28776 AN: 86220

European-Finnish (FIN) AF: 0.492 AC: 26194 AN: 53208

Middle Eastern (MID) AF: 0.549 AC: 3166 AN: 5764

European-Non Finnish (NFE) AF: 0.580 AC: 645141 AN: 1111784

Other (OTH) AF: 0.497 AC: 30033 AN: 60388

GnomAD4 genome AF: 0.431 AC: 65616 AN: 152222 Hom.: 16134 Cov.: 34 AF XY: 0.420 AC XY: 31289 AN XY: 74420

African (AFR) AF: 0.253 AC: 10508 AN: 41536

American (AMR) AF: 0.388 AC: 5930 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1772 AN: 3472

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5190

South Asian (SAS) AF: 0.316 AC: 1524 AN: 4828

European-Finnish (FIN) AF: 0.479 AC: 5076 AN: 10588

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39117 AN: 67994

Other (OTH) AF: 0.465 AC: 983 AN: 2112

Alfa AF: 0.499 Hom.: 6196

Bravo AF: 0.413

Asia WGS AF: 0.156 AC: 548 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.90
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3918253; hg19: chr20-44639511;