chr20-46009497-T-C

Position:

• chr20-46009497-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004994.3(MMP9):​c.139-369T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,842 control chromosomes in the GnomAD database, including 13,873 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (13873 hom., cov: 30)
• Consequence: MMP9 NM_004994.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP9	NM_004994.3	c.139-369T>C		intron_variant		ENST00000372330.3	NP_004985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3	c.139-369T>C		intron_variant		1	NM_004994.3	ENSP00000361405.3

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63125 AN: 151724 Hom.: 13867 Cov.: 30

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.416 AC: 63167 AN: 151842 Hom.: 13873 Cov.: 30 AF XY: 0.421 AC XY: 31245 AN XY: 74182

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.382

Alfa AF: 0.295 Hom.: 980

Bravo AF: 0.411

Asia WGS AF: 0.566 AC: 1965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.5
DANN	Benign	0.76

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: rs3918249; hg19: chr20-44638136;