rs3918253

chr20-46010872-C-T

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.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, single submitter B:1
• Conservation: PhyloP100: -0.194

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=-0.76).
• BP6: Variant 20-46010872-C-T is Benign according to our data. Variant chr20-46010872-C-T is described in ClinVar as [Benign]. Clinvar id is 1281057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP9	NM_004994.3	c.521-50C>T		intron_variant		ENST00000372330.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP9	ENST00000372330.3	c.521-50C>T		intron_variant		1	NM_004994.3	P1

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

GnomAD3 exomes AF: 0.425 AC: 105470 AN: 248058 Hom.: 26581 AF XY: 0.436 AC XY: 58533 AN XY: 134308

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 SAS exome AF: 0.329

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

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.00139

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.492

Gnomad4 NFE exome AF: 0.580

Gnomad4 OTH exome AF: 0.497

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

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.465

Alfa AF: 0.499 Hom.: 6196

Bravo AF: 0.413

Asia WGS AF: 0.156 AC: 548 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 12, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	11
Dann	Benign	0.90

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: rs3918253; hg19: chr20-44639511;