rs13969

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000372330.3(MMP9):c.1821A>C(p.Gly607=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,537,284 control chromosomes in the GnomAD database, including 257,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21915 hom., cov: 33)

Exomes 𝑓: 0.58 ( 235780 hom. )

Consequence

MMP9
ENST00000372330.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.24

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:

SLC12A5-AS1 (HGNC:53143): (SLC12A5 and MMP9 antisense RNA 1)

SLC12A5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 20-46014194-A-C is Benign according to our data. Variant chr20-46014194-A-C is described in ClinVar as [Benign]. Clinvar id is 285363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46014194-A-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP9	NM_004994.3 linkuse as main transcript	c.1821A>C	p.Gly607=	synonymous_variant	11/13	ENST00000372330.3	NP_004985.2
SLC12A5-AS1	NR_147699.1 linkuse as main transcript	n.1263T>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3 linkuse as main transcript	c.1821A>C	p.Gly607=	synonymous_variant	11/13	1	NM_004994.3	ENSP00000361405	P1
SLC12A5-AS1	ENST00000535913.2 linkuse as main transcript	n.1263T>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.528

AC:

80229

AN:

151966

Hom.:

21914

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.651

Gnomad AMR

AF:

0.542

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.540

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.555

GnomAD3 exomes

AF:

0.499

AC:

67779

AN:

135832

Hom.:

17974

AF XY:

0.497

AC XY:

36750

AN XY:

73898

show subpopulations

Gnomad AFR exome

AF:

0.415

Gnomad AMR exome

AF:

0.457

Gnomad ASJ exome

AF:

0.565

Gnomad EAS exome

AF:

0.246

Gnomad SAS exome

AF:

0.402

Gnomad FIN exome

AF:

0.533

Gnomad NFE exome

AF:

0.606

Gnomad OTH exome

AF:

0.543

GnomAD4 exome

AF:

0.577

AC:

799523

AN:

1385202

Hom.:

235780

Cov.:

AF XY:

0.573

AC XY:

391217

AN XY:

683186

show subpopulations

Gnomad4 AFR exome

AF:

0.423

Gnomad4 AMR exome

AF:

0.466

Gnomad4 ASJ exome

AF:

0.566

Gnomad4 EAS exome

AF:

0.239

Gnomad4 SAS exome

AF:

0.403

Gnomad4 FIN exome

AF:

0.547

Gnomad4 NFE exome

AF:

0.611

Gnomad4 OTH exome

AF:

0.561

GnomAD4 genome

AF:

0.528

AC:

80263

AN:

152082

Hom.:

21915

Cov.:

AF XY:

0.521

AC XY:

38745

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.433

Gnomad4 AMR

AF:

0.542

Gnomad4 ASJ

AF:

0.573

Gnomad4 EAS

AF:

0.238

Gnomad4 SAS

AF:

0.387

Gnomad4 FIN

AF:

0.540

Gnomad4 NFE

AF:

0.607

Gnomad4 OTH

AF:

0.549

Alfa

AF:

0.530

Hom.:

4186

Bravo

AF:

0.520

Asia WGS

AF:

0.317

AC:

1107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Metaphyseal anadysplasia 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 28, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.74

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

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