rs3918251

Variant names:

• chr20-46010142-A-G
• rs3918251
• NM_004994.3:c.371+44A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-46010142-A-G
• chr20-46010142-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.33
• Publications: 20 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]

MMP9 Gene-Disease associations (from GenCC):

• metaphyseal anadysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• metaphyseal anadysplasia 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1220806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 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.371+44A>G		intron	N/A	NP_004985.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP9	ENST00000372330.3	TSL:1 MANE Select	c.371+44A>G		intron	N/A	ENSP00000361405.3

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

GnomAD2 exomes AF: 0.410 AC: 56746 AN: 138244 AF XY: 0.422

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 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

African (AFR) AF: 0.480 AC: 13608 AN: 28338

American (AMR) AF: 0.249 AC: 8680 AN: 34918

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 9745 AN: 23390

East Asian (EAS) AF: 0.644 AC: 22329 AN: 34694

South Asian (SAS) AF: 0.508 AC: 37863 AN: 74546

European-Finnish (FIN) AF: 0.412 AC: 19167 AN: 46572

Middle Eastern (MID) AF: 0.359 AC: 1358 AN: 3784

European-Non Finnish (NFE) AF: 0.340 AC: 323816 AN: 952814

Other (OTH) AF: 0.382 AC: 20120 AN: 52676

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

African (AFR) AF: 0.476 AC: 19654 AN: 41304

American (AMR) AF: 0.293 AC: 4477 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1456 AN: 3468

East Asian (EAS) AF: 0.665 AC: 3399 AN: 5112

South Asian (SAS) AF: 0.536 AC: 2578 AN: 4806

European-Finnish (FIN) AF: 0.426 AC: 4478 AN: 10512

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24643 AN: 67860

Other (OTH) AF: 0.394 AC: 831 AN: 2108

Alfa AF: 0.359 Hom.: 4309

Bravo AF: 0.401

Asia WGS AF: 0.545 AC: 1896 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.17
PhyloP100		-1.3
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: rs3918251; hg19: chr20-44638781;