NM_004994.3:c.1174+7G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004994.3(MMP9):c.1174+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 1,612,638 control chromosomes in the GnomAD database, including 229,962 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 16140 hom., cov: 33)

Exomes 𝑓: 0.52 ( 213822 hom. )

Consequence

MMP9
NM_004994.3 splice_region, intron

Scores

Splicing: ADA: 0.00001118

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.572

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 20-46012320-G-A is Benign according to our data. Variant chr20-46012320-G-A is described in ClinVar as [Benign]. Clinvar id is 338554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46012320-G-A is described in Lovd as [Benign].

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 rank	MANE	Protein	UniProt
MMP9	NM_004994.3 link	c.1174+7G>A		splice_region_variant, intron_variant	Intron 7 of 12	ENST00000372330.3	NP_004985.2	P14780

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3 link	c.1174+7G>A		splice_region_variant, intron_variant	Intron 7 of 12	1	NM_004994.3	ENSP00000361405.3		P14780

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65607

AN:

152040

Hom.:

16145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.568

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.576

Gnomad OTH

AF:

0.471

GnomAD3 exomes

AF:

0.428

AC:

106041

AN:

247912

Hom.:

26860

AF XY:

0.438

AC XY:

58944

AN XY:

134698

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.512

Gnomad EAS exome

AF:

0.00231

Gnomad SAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.482

Gnomad NFE exome

AF:

0.579

Gnomad OTH exome

AF:

0.488

GnomAD4 exome

AF:

0.525

AC:

766383

AN:

1460480

Hom.:

213822

Cov.:

AF XY:

0.521

AC XY:

378728

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.237

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.508

Gnomad4 EAS exome

AF:

0.00141

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:

65608

AN:

152158

Hom.:

16140

Cov.:

AF XY:

0.421

AC XY:

31277

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.253

Gnomad4 AMR

AF:

0.388

Gnomad4 ASJ

AF:

0.510

Gnomad4 EAS

AF:

0.00405

Gnomad4 SAS

AF:

0.315

Gnomad4 FIN

AF:

0.480

Gnomad4 NFE

AF:

0.576

Gnomad4 OTH

AF:

0.466

Alfa

AF:

0.512

Hom.:

5525

Bravo

AF:

0.413

Asia WGS

AF:

0.156

AC:

547

AN:

3478

EpiCase

AF:

0.580

EpiControl

AF:

0.582

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 12, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Metaphyseal anadysplasia 2

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.3

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000011

dbscSNV1_RF

Benign

0.0020

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

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