rs3918251

chr20-46010142-A-Gchr20-46010142-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004994.3(MMP9):c.371+44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,403,370 control chromosomes in the GnomAD database, including 104,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13116 hom., cov: 29)
  • Exomes 𝑓: 0.36 (91646 hom.)
• Consequence: MMP9 NM_004994.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 20-46010142-A-G is Benign according to our data. Variant chr20-46010142-A-G is described in ClinVar as [Benign]. Clinvar id is 1220806.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP9	NM_004994.3	c.371+44A>G		intron_variant		ENST00000372330.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP9	ENST00000372330.3	c.371+44A>G		intron_variant		1	NM_004994.3	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61867 AN: 151520 Hom.: 13093 Cov.: 29

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.394

GnomAD3 exomes AF: 0.410 AC: 56746 AN: 138244 Hom.: 12696 AF XY: 0.422 AC XY: 31530 AN XY: 74752

Gnomad AFR exome AF: 0.484

Gnomad AMR exome AF: 0.246

Gnomad ASJ exome AF: 0.425

Gnomad EAS exome AF: 0.690

Gnomad SAS exome AF: 0.519

Gnomad FIN exome AF: 0.427

Gnomad NFE exome AF: 0.367

Gnomad OTH exome AF: 0.393

GnomAD4 exome AF: 0.365 AC: 456686 AN: 1251732 Hom.: 91646 Cov.: 20 AF XY: 0.371 AC XY: 230228 AN XY: 621296

Gnomad4 AFR exome AF: 0.480

Gnomad4 AMR exome AF: 0.249

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.644

Gnomad4 SAS exome AF: 0.508

Gnomad4 FIN exome AF: 0.412

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.408 AC: 61933 AN: 151638 Hom.: 13116 Cov.: 29 AF XY: 0.414 AC XY: 30679 AN XY: 74078

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.394

Alfa AF: 0.351 Hom.: 2747

Bravo AF: 0.401

Asia WGS AF: 0.545 AC: 1896 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.17
Dann	Benign	0.17

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: rs3918251; hg19: chr20-44638781;