rs11225308

Variant names:

• chr11-102528747-T-G
• rs11225308
• NM_002423.5:c.109-764A>C

Variant summary

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

The NM_002423.5(MMP7):​c.109-764A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,102 control chromosomes in the GnomAD database, including 4,223 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 0.23 (4223 hom., cov: 32)
• Consequence: MMP7 NM_002423.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 15 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP7	NM_002423.5	c.109-764A>C		intron_variant	Intron 1 of 5	ENST00000260227.5	NP_002414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP7	ENST00000260227.5	c.109-764A>C		intron_variant	Intron 1 of 5	1	NM_002423.5	ENSP00000260227.4
MMP7	ENST00000531200.1	n.156-764A>C		intron_variant	Intron 1 of 2	2
MMP7	ENST00000533366.5	n.159-764A>C		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35608 AN: 151984 Hom.: 4214 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.234 AC: 35655 AN: 152102 Hom.: 4223 Cov.: 32 AF XY: 0.229 AC XY: 17021 AN XY: 74362

African (AFR) AF: 0.262 AC: 10859 AN: 41498

American (AMR) AF: 0.201 AC: 3068 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1198 AN: 5178

South Asian (SAS) AF: 0.0942 AC: 455 AN: 4828

European-Finnish (FIN) AF: 0.220 AC: 2325 AN: 10586

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16097 AN: 67964

Other (OTH) AF: 0.237 AC: 499 AN: 2106

Alfa AF: 0.241 Hom.: 1379

Bravo AF: 0.236

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.1
DANN	Benign	0.75
PhyloP100		-0.085
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: rs11225308; hg19: chr11-102399478;