rs12447804

Variant names:

• chr16-58041378-C-T
• rs12447804
• NM_002428.4:c.911-239C>T

Variant summary

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

The NM_002428.4(MMP15):​c.911-239C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,116 control chromosomes in the GnomAD database, including 3,351 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 0.19 (3351 hom., cov: 33)
• Consequence: MMP15 NM_002428.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• Publications: 38 publications found

Genes affected

MMP15 (HGNC:7161): (matrix metallopeptidase 15) This gene encodes a member of the peptidase M10 family and membrane-type subfamily 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. Members of this subfamily contain a transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. The encoded preproprotein is proteolytically processed to generate the mature protease. This protein may play a role in cancer progression. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP15	NM_002428.4	c.911-239C>T		intron_variant	Intron 5 of 9	ENST00000219271.4	NP_002419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP15	ENST00000219271.4	c.911-239C>T		intron_variant	Intron 5 of 9	1	NM_002428.4	ENSP00000219271.3

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28216 AN: 151998 Hom.: 3342 Cov.: 33

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.186 AC: 28237 AN: 152116 Hom.: 3351 Cov.: 33 AF XY: 0.193 AC XY: 14345 AN XY: 74360

African (AFR) AF: 0.0603 AC: 2503 AN: 41532

American (AMR) AF: 0.303 AC: 4637 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3472

East Asian (EAS) AF: 0.349 AC: 1800 AN: 5156

South Asian (SAS) AF: 0.173 AC: 836 AN: 4822

European-Finnish (FIN) AF: 0.312 AC: 3308 AN: 10594

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14176 AN: 67930

Other (OTH) AF: 0.170 AC: 359 AN: 2112

Alfa AF: 0.200 Hom.: 8281

Bravo AF: 0.184

Asia WGS AF: 0.257 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.043
DANN	Benign	0.70
PhyloP100		-2.0
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: rs12447804; hg19: chr16-58075282;