rs14983

Positions:

• chr11-102520694-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• 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/exons	MANE	Protein	UniProt
MMP7	NM_002423.5	c.*82C>T		3_prime_UTR_variant	6/6	ENST00000260227.5	NP_002414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP7	ENST00000260227.5	c.*82C>T		3_prime_UTR_variant	6/6	1	NM_002423.5	ENSP00000260227	P1

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

Gnomad4 AFR exome AF: 0.0321

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.217

Gnomad4 SAS exome AF: 0.0976

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.194

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

Gnomad4 AFR AF: 0.0387

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.0923

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.173

Alfa AF: 0.204 Hom.: 3411

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

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: rs14983; hg19: chr11-102391425;