11-102526865-A-G

Variant summary

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

The NM_002423.5(MMP7):c.484+659T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,394 control chromosomes in the GnomAD database, including 2,520 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 0.16 (2519 hom., cov: 31)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: MMP7 NM_002423.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP7	NM_002423.5	c.484+659T>C		intron_variant		ENST00000260227.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP7	ENST00000260227.5	c.484+659T>C		intron_variant		1	NM_002423.5	P1
MMP7	ENST00000533366.5	n.534+659T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24993 AN: 152052 Hom.: 2518 Cov.: 31

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.0922

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.152 AC: 34 AN: 224 Hom.: 1 AF XY: 0.118 AC XY: 17 AN XY: 144

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0556

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.164 AC: 24998 AN: 152170 Hom.: 2519 Cov.: 31 AF XY: 0.161 AC XY: 11998 AN XY: 74392

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.0929

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.178

Alfa AF: 0.193 Hom.: 519

Bravo AF: 0.156

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.2
Dann	Benign	0.35

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: rs11225307; hg19: chr11-102397596;