20-46014953-A-G

Variant names:

• chr20-46014953-A-G
• rs3918261
• NM_004994.3:c.2005+479A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004994.3(MMP9):​c.2005+479A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,158 control chromosomes in the GnomAD database, including 2,125 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 0.16 (2125 hom., cov: 32)
• Consequence: MMP9 NM_004994.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 30 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP9	NM_004994.3	MANE Select	c.2005+479A>G		intron	N/A	NP_004985.2
	SLC12A5-AS1	NR_147699.1		n.669-165T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP9	ENST00000372330.3	TSL:1 MANE Select	c.2005+479A>G		intron	N/A	ENSP00000361405.3
	SLC12A5-AS1	ENST00000535913.2	TSL:2	n.669-165T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24753 AN: 152040 Hom.: 2127 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.0959

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.163 AC: 24775 AN: 152158 Hom.: 2125 Cov.: 32 AF XY: 0.164 AC XY: 12222 AN XY: 74398

African (AFR) AF: 0.200 AC: 8282 AN: 41504

American (AMR) AF: 0.0957 AC: 1464 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3472

East Asian (EAS) AF: 0.148 AC: 766 AN: 5176

South Asian (SAS) AF: 0.298 AC: 1436 AN: 4814

European-Finnish (FIN) AF: 0.170 AC: 1804 AN: 10602

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

European-Non Finnish (NFE) AF: 0.148 AC: 10029 AN: 67978

Other (OTH) AF: 0.159 AC: 335 AN: 2112

Alfa AF: 0.160 Hom.: 1133

Bravo AF: 0.156

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.45
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.31		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3918261; hg19: chr20-44643592; COSMIC: COSV63434649;