rs11568819

Variant names:

• chr11-102530902-G-A
• rs11568819
• NM_002423.5:c.-202C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002423.5(MMP7):​c.-202C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 497,540 control chromosomes in the GnomAD database, including 775 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 0.054 (246 hom., cov: 32)
  • Exomes 𝑓: 0.049 (529 hom.)
• Consequence: MMP7 NM_002423.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 39 publications found

Genes affected

MMP7 (HGNC:7174): (matrix metallopeptidase 7) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this 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. The encoded preproprotein is proteolytically processed to generate the mature protease. This secreted protease breaks down proteoglycans, fibronectin, elastin and casein and differs from most MMP family members in that it lacks a conserved C-terminal hemopexin domain. The enzyme is involved in wound healing, and studies in mice suggest that it regulates the activity of defensins in intestinal mucosa. The gene is part of a cluster of MMP genes on chromosome 11. This gene exhibits elevated expression levels in multiple human cancers. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002423.5. 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
	MMP7	NM_002423.5	MANE Select	c.-202C>T		upstream_gene	N/A	NP_002414.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP7	ENST00000260227.5	TSL:1 MANE Select	c.-202C>T		upstream_gene	N/A	ENSP00000260227.4
	MMP7	ENST00000531200.1	TSL:2	n.-155C>T		upstream_gene	N/A
	MMP7	ENST00000533366.5	TSL:2	n.-152C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 8215 AN: 151978 Hom.: 247 Cov.: 32

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.0365

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0502

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0636

Gnomad OTH AF: 0.0511

GnomAD4 exome AF: 0.0491 AC: 16963 AN: 345446 Hom.: 529 AF XY: 0.0488 AC XY: 8891 AN XY: 182016

African (AFR) AF: 0.0462 AC: 426 AN: 9212

American (AMR) AF: 0.0296 AC: 335 AN: 11312

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 303 AN: 10946

East Asian (EAS) AF: 0.000349 AC: 8 AN: 22908

South Asian (SAS) AF: 0.0458 AC: 1721 AN: 37600

European-Finnish (FIN) AF: 0.0552 AC: 1146 AN: 20746

Middle Eastern (MID) AF: 0.0631 AC: 102 AN: 1616

European-Non Finnish (NFE) AF: 0.0568 AC: 11980 AN: 211012

Other (OTH) AF: 0.0469 AC: 942 AN: 20094

GnomAD4 genome AF: 0.0541 AC: 8221 AN: 152094 Hom.: 246 Cov.: 32 AF XY: 0.0538 AC XY: 3998 AN XY: 74344

African (AFR) AF: 0.0503 AC: 2086 AN: 41494

American (AMR) AF: 0.0364 AC: 557 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0500 AC: 241 AN: 4816

European-Finnish (FIN) AF: 0.0553 AC: 583 AN: 10544

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0636 AC: 4325 AN: 67978

Other (OTH) AF: 0.0501 AC: 106 AN: 2114

Alfa AF: 0.0551 Hom.: 143

Bravo AF: 0.0527

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		-1.1
PromoterAI		0.51	Over-expression
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs11568819; hg19: chr11-102401633;