20-46009713-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004994.3(MMP9):c.139-153A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 152,170 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.015 (129 hom., cov: 31)
• Consequence: MMP9 NM_004994.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.15

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-46009713-A-G is Benign according to our data. Variant chr20-46009713-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1198083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP9	NM_004994.3	c.139-153A>G		intron_variant		ENST00000372330.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP9	ENST00000372330.3	c.139-153A>G		intron_variant		1	NM_004994.3	P1

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2232 AN: 152052 Hom.: 130 Cov.: 31

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.00970

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0146 AC: 2227 AN: 152170 Hom.: 129 Cov.: 31 AF XY: 0.0167 AC XY: 1242 AN XY: 74424

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.0410

Gnomad4 FIN AF: 0.00970

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.000490 Hom.: 0

Bravo AF: 0.0160

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.7
Dann	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs3918250; hg19: chr20-44638352; COSMIC: COSV64885936; COSMIC: COSV64885936;