rs14983

Variant names:

• chr11-102520694-G-A
• rs14983
• NM_002423.5:c.*82C>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.*82C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,163,144 control chromosomes in the GnomAD database, including 25,247 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 (2413 hom., cov: 32)
  • Exomes 𝑓: 0.20 (22834 hom.)
• Consequence: MMP7 NM_002423.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 18 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP7	NM_002423.5	c.*82C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000260227.5	NP_002414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP7	ENST00000260227.5	c.*82C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_002423.5	ENSP00000260227.4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24397 AN: 151996 Hom.: 2412 Cov.: 32

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.205 AC: 207164 AN: 1011030 Hom.: 22834 Cov.: 13 AF XY: 0.202 AC XY: 103958 AN XY: 514094

African (AFR) AF: 0.0321 AC: 761 AN: 23712

American (AMR) AF: 0.152 AC: 4532 AN: 29828

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 4604 AN: 20124

East Asian (EAS) AF: 0.217 AC: 7975 AN: 36834

South Asian (SAS) AF: 0.0976 AC: 6488 AN: 66454

European-Finnish (FIN) AF: 0.234 AC: 8585 AN: 36676

Middle Eastern (MID) AF: 0.144 AC: 687 AN: 4780

European-Non Finnish (NFE) AF: 0.220 AC: 164819 AN: 747798

Other (OTH) AF: 0.194 AC: 8713 AN: 44824

GnomAD4 genome AF: 0.160 AC: 24402 AN: 152114 Hom.: 2413 Cov.: 32 AF XY: 0.158 AC XY: 11715 AN XY: 74346

African (AFR) AF: 0.0387 AC: 1608 AN: 41510

American (AMR) AF: 0.161 AC: 2456 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 779 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1198 AN: 5180

South Asian (SAS) AF: 0.0923 AC: 445 AN: 4820

European-Finnish (FIN) AF: 0.210 AC: 2212 AN: 10552

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.223 AC: 15134 AN: 67982

Other (OTH) AF: 0.173 AC: 366 AN: 2110

Alfa AF: 0.204 Hom.: 4427

Bravo AF: 0.152

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.86
DANN	Benign	0.20
PhyloP100		-0.097
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: rs14983; hg19: chr11-102391425;