rs28733439

Positions:

• chr16-58037359-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.163-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,374,472 control chromosomes in the GnomAD database, including 2,209 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 0.049 (181 hom., cov: 33)
  • Exomes 𝑓: 0.054 (2028 hom.)
• Consequence: MMP15 NM_002428.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP15	NM_002428.4	c.163-113C>T		intron_variant		ENST00000219271.4	NP_002419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP15	ENST00000219271.4	c.163-113C>T		intron_variant		1	NM_002428.4	ENSP00000219271.3

Frequencies

GnomAD3 genomes AF: 0.0487 AC: 7408 AN: 152110 Hom.: 180 Cov.: 33

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0462

Gnomad ASJ AF: 0.0665

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.0603

GnomAD4 exome AF: 0.0542 AC: 66249 AN: 1222244 Hom.: 2028 AF XY: 0.0542 AC XY: 32925 AN XY: 607402

Gnomad4 AFR exome AF: 0.0496

Gnomad4 AMR exome AF: 0.0339

Gnomad4 ASJ exome AF: 0.0719

Gnomad4 EAS exome AF: 0.000236

Gnomad4 SAS exome AF: 0.0441

Gnomad4 FIN exome AF: 0.0287

Gnomad4 NFE exome AF: 0.0587

Gnomad4 OTH exome AF: 0.0557

GnomAD4 genome AF: 0.0487 AC: 7415 AN: 152228 Hom.: 181 Cov.: 33 AF XY: 0.0471 AC XY: 3509 AN XY: 74424

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.0462

Gnomad4 ASJ AF: 0.0665

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0418

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0568

Gnomad4 OTH AF: 0.0601

Alfa AF: 0.0494 Hom.: 27

Bravo AF: 0.0499

Asia WGS AF: 0.0230 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.40
DANN	Benign	0.49

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: rs28733439; hg19: chr16-58071263;