20-46013092-G-A

Variant names:

• chr20-46013092-G-A
• rs3787268
• NM_004994.3:c.1331-163G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004994.3(MMP9):​c.1331-163G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 151,524 control chromosomes in the GnomAD database, including 2,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2703 hom., cov: 32)
• Consequence: MMP9 NM_004994.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.337
• Publications: 65 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 20-46013092-G-A is Benign according to our data. Variant chr20-46013092-G-A is described in ClinVar as Benign. ClinVar VariationId is 1263713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP9	NM_004994.3	c.1331-163G>A		intron_variant	Intron 8 of 12	ENST00000372330.3	NP_004985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3	c.1331-163G>A		intron_variant	Intron 8 of 12	1	NM_004994.3	ENSP00000361405.3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26877 AN: 151404 Hom.: 2700 Cov.: 32

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.177 AC: 26885 AN: 151524 Hom.: 2703 Cov.: 32 AF XY: 0.181 AC XY: 13422 AN XY: 74024

African (AFR) AF: 0.0882 AC: 3645 AN: 41310

American (AMR) AF: 0.156 AC: 2387 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3466

East Asian (EAS) AF: 0.397 AC: 1937 AN: 4884

South Asian (SAS) AF: 0.178 AC: 854 AN: 4786

European-Finnish (FIN) AF: 0.237 AC: 2498 AN: 10560

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14115 AN: 67948

Other (OTH) AF: 0.173 AC: 364 AN: 2100

Alfa AF: 0.119 Hom.: 236

Bravo AF: 0.169

Asia WGS AF: 0.223 AC: 771 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.39
PhyloP100		-0.34
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: rs3787268; hg19: chr20-44641731;