rs2250889

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004994.3(MMP9):c.1721G>C(p.Arg574Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 1,613,230 control chromosomes in the GnomAD database, including 697,146 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R574L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.90 ( 61725 hom., cov: 34)

Exomes 𝑓: 0.93 ( 635421 hom. )

Consequence

MMP9
NM_004994.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.934

Publications

173 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.9859115E-7).

BP6

Variant 20-46013767-G-C is Benign according to our data. Variant chr20-46013767-G-C is described in ClinVar as Benign. ClinVar VariationId is 282093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004994.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP9	NM_004994.3	MANE Select	c.1721G>C	p.Arg574Pro	missense	Exon 10 of 13	NP_004985.2	P14780
	SLC12A5-AS1	NR_147699.1		n.1690C>G		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MMP9	ENST00000372330.3	TSL:1 MANE Select	c.1721G>C	p.Arg574Pro	missense	Exon 10 of 13	ENSP00000361405.3	P14780
MMP9	ENST00000898203.1		c.1658G>C	p.Arg553Pro	missense	Exon 10 of 13	ENSP00000568262.1
MMP9	ENST00000898204.1		c.1592G>C	p.Arg531Pro	missense	Exon 9 of 12	ENSP00000568263.1

Frequencies

GnomAD3 genomes

AF:

0.897

AC:

136526

AN:

152144

Hom.:

61705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.845

Gnomad AMI

AF:

0.991

Gnomad AMR

AF:

0.808

Gnomad ASJ

AF:

0.952

Gnomad EAS

AF:

0.760

Gnomad SAS

AF:

0.859

Gnomad FIN

AF:

0.916

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.955

Gnomad OTH

AF:

0.903

GnomAD2 exomes

AF:

0.876

AC:

219719

AN:

250788

AF XY:

0.887

show subpopulations

Gnomad AFR exome

AF:

0.847

Gnomad AMR exome

AF:

0.643

Gnomad ASJ exome

AF:

0.959

Gnomad EAS exome

AF:

0.778

Gnomad FIN exome

AF:

0.918

Gnomad NFE exome

AF:

0.954

Gnomad OTH exome

AF:

0.907

GnomAD4 exome

AF:

0.930

AC:

1358563

AN:

1460968

Hom.:

635421

Cov.:

AF XY:

0.929

AC XY:

675346

AN XY:

726778

show subpopulations

African (AFR)

AF:

0.842

AC:

28173

AN:

33456

American (AMR)

AF:

0.663

AC:

29603

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.955

AC:

24952

AN:

26130

East Asian (EAS)

AF:

0.737

AC:

29250

AN:

39694

South Asian (SAS)

AF:

0.860

AC:

74107

AN:

86214

European-Finnish (FIN)

AF:

0.919

AC:

49086

AN:

53402

Middle Eastern (MID)

AF:

0.920

AC:

4722

AN:

5130

European-Non Finnish (NFE)

AF:

0.956

AC:

1062821

AN:

1111956

Other (OTH)

AF:

0.926

AC:

55849

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

5847

11694

17540

23387

29234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21554

43108

64662

86216

107770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.897

AC:

136587

AN:

152262

Hom.:

61725

Cov.:

AF XY:

0.893

AC XY:

66455

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.845

AC:

35108

AN:

41548

American (AMR)

AF:

0.808

AC:

12360

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.952

AC:

3305

AN:

3472

East Asian (EAS)

AF:

0.759

AC:

3896

AN:

5136

South Asian (SAS)

AF:

0.860

AC:

4153

AN:

4830

European-Finnish (FIN)

AF:

0.916

AC:

9731

AN:

10624

Middle Eastern (MID)

AF:

0.949

AC:

279

AN:

294

European-Non Finnish (NFE)

AF:

0.955

AC:

64952

AN:

68028

Other (OTH)

AF:

0.898

AC:

1899

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

685

1371

2056

2742

3427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.938

Hom.:

45699

Bravo

AF:

0.884

TwinsUK

AF:

0.959

AC:

3555

ALSPAC

AF:

0.955

AC:

3680

ESP6500AA

AF:

0.855

AC:

3767

ESP6500EA

AF:

0.953

AC:

8198

ExAC

AF:

0.883

AC:

107267

Asia WGS

AF:

0.755

AC:

2626

AN:

3478

EpiCase

AF:

0.955

EpiControl

AF:

0.954

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Metaphyseal anadysplasia 2 (3)

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.049

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.093

MetaRNN

Benign

8.0e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.5

PhyloP100

0.93

PrimateAI

Benign

0.35

PROVEAN

Benign

3.9

REVEL

Benign

0.053

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.041

ClinPred

0.012

GERP RS

3.9

Varity_R

0.12

gMVP

0.74

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over