rs2274755

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004994.3(MMP9):c.649+3G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,514 control chromosomes in the GnomAD database, including 20,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1883 hom., cov: 33)

Exomes 𝑓: 0.15 ( 18137 hom. )

Consequence

MMP9
NM_004994.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.9652

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.22

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 20-46011053-G-T is Benign according to our data. Variant chr20-46011053-G-T is described in ClinVar as [Benign]. Clinvar id is 338548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP9	NM_004994.3 linkuse as main transcript	c.649+3G>T		splice_donor_region_variant, intron_variant		ENST00000372330.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP9	ENST00000372330.3 linkuse as main transcript	c.649+3G>T		splice_donor_region_variant, intron_variant		1	NM_004994.3	P1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23398

AN:

152084

Hom.:

1885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0934

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.154

AC:

38552

AN:

250870

Hom.:

3437

AF XY:

0.163

AC XY:

22093

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.0644

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.130

Gnomad SAS exome

AF:

0.291

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.152

AC:

222093

AN:

1461312

Hom.:

18137

Cov.:

AF XY:

0.157

AC XY:

113780

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.0693

Gnomad4 ASJ exome

AF:

0.159

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.143

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.154

AC:

23415

AN:

152202

Hom.:

1883

Cov.:

AF XY:

0.155

AC XY:

11565

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.0932

Gnomad4 ASJ

AF:

0.158

Gnomad4 EAS

AF:

0.143

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.143

Hom.:

2139

Bravo

AF:

0.146

Asia WGS

AF:

0.205

AC:

712

AN:

3478

EpiCase

AF:

0.149

EpiControl

AF:

0.142

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Metaphyseal anadysplasia 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 16631427, 25525159) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 10, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

Cadd

Benign

Dann

Benign

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.97

dbscSNV1_RF

Benign

0.30

SpliceAI score (max)

0.34

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.34

Position offset: -3

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over