rs28733439

Variant names:

• chr16-58037359-C-T
• rs28733439
• NM_002428.4:c.163-113C>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.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
• Publications: 2 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=-0.92).
• 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 rank	MANE	Protein	UniProt
MMP15	NM_002428.4	c.163-113C>T		intron_variant	Intron 1 of 9	ENST00000219271.4	NP_002419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP15	ENST00000219271.4	c.163-113C>T		intron_variant	Intron 1 of 9	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

African (AFR) AF: 0.0496 AC: 1408 AN: 28404

American (AMR) AF: 0.0339 AC: 1216 AN: 35866

Ashkenazi Jewish (ASJ) AF: 0.0719 AC: 1453 AN: 20206

East Asian (EAS) AF: 0.000236 AC: 9 AN: 38212

South Asian (SAS) AF: 0.0441 AC: 3096 AN: 70156

European-Finnish (FIN) AF: 0.0287 AC: 1309 AN: 45548

Middle Eastern (MID) AF: 0.0939 AC: 406 AN: 4324

European-Non Finnish (NFE) AF: 0.0587 AC: 54473 AN: 927822

Other (OTH) AF: 0.0557 AC: 2879 AN: 51706

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

African (AFR) AF: 0.0467 AC: 1939 AN: 41538

American (AMR) AF: 0.0462 AC: 706 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0665 AC: 231 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0418 AC: 201 AN: 4814

European-Finnish (FIN) AF: 0.0303 AC: 321 AN: 10602

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0568 AC: 3866 AN: 68004

Other (OTH) AF: 0.0601 AC: 127 AN: 2112

Alfa AF: 0.0502 Hom.: 92

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
PhyloP100		-3.0
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: rs28733439; hg19: chr16-58071263;