rs11568819

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP7	NM_002423.5	c.-202C>T		upstream_gene_variant		ENST00000260227.5	NP_002414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP7	ENST00000260227.5	c.-202C>T		upstream_gene_variant		1	NM_002423.5	ENSP00000260227.4
MMP7	ENST00000531200.1	n.-155C>T		upstream_gene_variant		2
MMP7	ENST00000533366.5	n.-152C>T		upstream_gene_variant		2

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

Gnomad4 AFR exome AF: 0.0462

Gnomad4 AMR exome AF: 0.0296

Gnomad4 ASJ exome AF: 0.0277

Gnomad4 EAS exome AF: 0.000349

Gnomad4 SAS exome AF: 0.0458

Gnomad4 FIN exome AF: 0.0552

Gnomad4 NFE exome AF: 0.0568

Gnomad4 OTH exome AF: 0.0469

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

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.0364

Gnomad4 ASJ AF: 0.0331

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0500

Gnomad4 FIN AF: 0.0553

Gnomad4 NFE AF: 0.0636

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0561 Hom.: 75

Bravo AF: 0.0527

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11568819; hg19: chr11-102401633;