chr20-46015131-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004994.3(MMP9):​c.2005+657A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,102 control chromosomes in the GnomAD database, including 2,727 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2727 hom., cov: 32)

Consequence

MMP9
NM_004994.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.939

Publications

15 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]
SLC12A5-AS1 (HGNC:53143): (SLC12A5 and MMP9 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MMP9NM_004994.3 linkc.2005+657A>G intron_variant Intron 12 of 12 ENST00000372330.3 NP_004985.2 P14780
SLC12A5-AS1NR_147699.1 linkn.669-343T>C intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MMP9ENST00000372330.3 linkc.2005+657A>G intron_variant Intron 12 of 12 1 NM_004994.3 ENSP00000361405.3 P14780
SLC12A5-AS1ENST00000535913.2 linkn.669-343T>C intron_variant Intron 2 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.177
AC:
26895
AN:
151984
Hom.:
2724
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0871
Gnomad AMI
AF:
0.261
Gnomad AMR
AF:
0.156
Gnomad ASJ
AF:
0.229
Gnomad EAS
AF:
0.387
Gnomad SAS
AF:
0.177
Gnomad FIN
AF:
0.236
Gnomad MID
AF:
0.193
Gnomad NFE
AF:
0.207
Gnomad OTH
AF:
0.177
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.177
AC:
26902
AN:
152102
Hom.:
2727
Cov.:
32
AF XY:
0.181
AC XY:
13437
AN XY:
74336
show subpopulations
African (AFR)
AF:
0.0873
AC:
3626
AN:
41526
American (AMR)
AF:
0.156
AC:
2387
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.229
AC:
795
AN:
3470
East Asian (EAS)
AF:
0.387
AC:
1996
AN:
5164
South Asian (SAS)
AF:
0.178
AC:
856
AN:
4818
European-Finnish (FIN)
AF:
0.236
AC:
2488
AN:
10558
Middle Eastern (MID)
AF:
0.184
AC:
54
AN:
294
European-Non Finnish (NFE)
AF:
0.207
AC:
14094
AN:
67960
Other (OTH)
AF:
0.174
AC:
368
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1099
2197
3296
4394
5493
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
304
608
912
1216
1520
<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:
0.127
Hom.:
269
Bravo
AF:
0.169
Asia WGS
AF:
0.235
AC:
815
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
14
DANN
Benign
0.82
PhyloP100
0.94
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs3918262; hg19: chr20-44643770; API