rs13925

Variant names:

• chr20-46016326-G-A
• rs13925
• NM_004994.3:c.2082G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004994.3(MMP9):​c.2082G>A​(p.Val694Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,613,864 control chromosomes in the GnomAD database, including 18,445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1672 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16773 hom.)
• Consequence: MMP9 NM_004994.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.58
• Publications: 46 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 20-46016326-G-A is Benign according to our data. Variant chr20-46016326-G-A is described in ClinVar as Benign. ClinVar VariationId is 338561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.58 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 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.2082G>A	p.Val694Val	synonymous	Exon 13 of 13	NP_004985.2	P14780
	SLC12A5-AS1	NR_147699.1		n.669-1538C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP9	ENST00000372330.3	TSL:1 MANE Select	c.2082G>A	p.Val694Val	synonymous	Exon 13 of 13	ENSP00000361405.3	P14780
	MMP9	ENST00000898203.1		c.2019G>A	p.Val673Val	synonymous	Exon 13 of 13	ENSP00000568262.1
	MMP9	ENST00000898204.1		c.1953G>A	p.Val651Val	synonymous	Exon 12 of 12	ENSP00000568263.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22200 AN: 152014 Hom.: 1672 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.0919

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.144

GnomAD2 exomes AF: 0.146 AC: 36588 AN: 251428 AF XY: 0.153

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.0637

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.131

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.148 AC: 216641 AN: 1461732 Hom.: 16773 Cov.: 34 AF XY: 0.151 AC XY: 110164 AN XY: 727182

African (AFR) AF: 0.147 AC: 4929 AN: 33472

American (AMR) AF: 0.0685 AC: 3065 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 4150 AN: 26134

East Asian (EAS) AF: 0.162 AC: 6414 AN: 39698

South Asian (SAS) AF: 0.233 AC: 20081 AN: 86254

European-Finnish (FIN) AF: 0.165 AC: 8790 AN: 53420

Middle Eastern (MID) AF: 0.152 AC: 876 AN: 5768

European-Non Finnish (NFE) AF: 0.143 AC: 158883 AN: 1111874

Other (OTH) AF: 0.157 AC: 9453 AN: 60390

GnomAD4 genome AF: 0.146 AC: 22213 AN: 152132 Hom.: 1672 Cov.: 32 AF XY: 0.146 AC XY: 10894 AN XY: 74376

African (AFR) AF: 0.147 AC: 6105 AN: 41488

American (AMR) AF: 0.0916 AC: 1401 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 544 AN: 3470

East Asian (EAS) AF: 0.148 AC: 765 AN: 5172

South Asian (SAS) AF: 0.234 AC: 1130 AN: 4820

European-Finnish (FIN) AF: 0.170 AC: 1803 AN: 10596

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10041 AN: 67986

Other (OTH) AF: 0.148 AC: 311 AN: 2108

Alfa AF: 0.142 Hom.: 4723

Bravo AF: 0.139

Asia WGS AF: 0.181 AC: 628 AN: 3478

EpiCase AF: 0.148

EpiControl AF: 0.141

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Metaphyseal anadysplasia 2 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.2
DANN	Benign	0.76
PhyloP100		1.6
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

Other links and lift over

dbSNP: rs13925; hg19: chr20-44644965; COSMIC: COSV63433827; COSMIC: COSV63433827;