rs3918262

Positions:

• chr20-46015131-A-G
• chr20-46015131-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MMP9	NM_004994.3	c.2005+657A>G		intron_variant		ENST00000372330.3	NP_004985.2
SLC12A5-AS1	NR_147699.1	n.669-343T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP9	ENST00000372330.3	c.2005+657A>G		intron_variant		1	NM_004994.3	ENSP00000361405	P1
SLC12A5-AS1	ENST00000535913.2	n.669-343T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26895 AN: 151984 Hom.: 2724 Cov.: 32

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

Gnomad4 AFR AF: 0.0873

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.174

Alfa AF: 0.129 Hom.: 265

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

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

LitVar

Other links and lift over

dbSNP: rs3918262; hg19: chr20-44643770;