20-46014194-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004994.3(MMP9):c.1821A>C(p.Gly607Gly) 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
NM_004994.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.24

Publications

32 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 -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 VariationId is 285363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
MMP9	NM_004994.3 link	c.1821A>C	p.Gly607Gly	synonymous_variant	Exon 11 of 13	ENST00000372330.3	NP_004985.2	P14780
SLC12A5-AS1	NR_147699.1 link	n.1263T>G		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3 link	c.1821A>C	p.Gly607Gly	synonymous_variant	Exon 11 of 13	1	NM_004994.3	ENSP00000361405.3		P14780
SLC12A5-AS1	ENST00000535913.2 link	n.1263T>G		non_coding_transcript_exon_variant	Exon 3 of 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

GnomAD2 exomes

AF:

0.499

AC:

67779

AN:

135832

AF XY:

0.497

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 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

African (AFR)

AF:

0.423

AC:

13302

AN:

31436

American (AMR)

AF:

0.466

AC:

16507

AN:

35394

Ashkenazi Jewish (ASJ)

AF:

0.566

AC:

14180

AN:

25056

East Asian (EAS)

AF:

0.239

AC:

8538

AN:

35672

South Asian (SAS)

AF:

0.403

AC:

31842

AN:

79006

European-Finnish (FIN)

AF:

0.547

AC:

21614

AN:

39494

Middle Eastern (MID)

AF:

0.589

AC:

2871

AN:

4878

European-Non Finnish (NFE)

AF:

0.611

AC:

658348

AN:

1076632

Other (OTH)

AF:

0.561

AC:

32321

AN:

57634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

20000

39999

59999

79998

99998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17864

35728

53592

71456

89320

<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:

0.528

AC:

80263

AN:

152082

Hom.:

21915

Cov.:

AF XY:

0.521

AC XY:

38745

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.433

AC:

17978

AN:

41498

American (AMR)

AF:

0.542

AC:

8282

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

1989

AN:

3470

East Asian (EAS)

AF:

0.238

AC:

1227

AN:

5148

South Asian (SAS)

AF:

0.387

AC:

1863

AN:

4818

European-Finnish (FIN)

AF:

0.540

AC:

5720

AN:

10590

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.607

AC:

41276

AN:

67952

Other (OTH)

AF:

0.549

AC:

1160

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1938

3876

5813

7751

9689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.530

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Metaphyseal anadysplasia 2

Benign:2

Jan 12, 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. -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jun 28, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

-2.2

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over