rs3918261

Positions:

• chr20-46014953-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP9	NM_004994.3	c.2005+479A>G		intron_variant		ENST00000372330.3	NP_004985.2
SLC12A5-AS1	NR_147699.1	n.669-165T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3	c.2005+479A>G		intron_variant		1	NM_004994.3	ENSP00000361405.3
SLC12A5-AS1	ENST00000535913.2	n.669-165T>C		intron_variant		2

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

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.0957

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.159

Alfa AF: 0.161 Hom.: 1039

Bravo AF: 0.156

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

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