rs12447804

chr16-58041378-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MMP15	NM_002428.4	c.911-239C>T		intron_variant		ENST00000219271.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP15	ENST00000219271.4	c.911-239C>T		intron_variant		1	NM_002428.4	P1

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

Gnomad4 AFR AF: 0.0603

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.170

Alfa AF: 0.203 Hom.: 2452

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

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: rs12447804; hg19: chr16-58075282;