16-58040306-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002428.4(MMP15):c.748+124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,091,612 control chromosomes in the GnomAD database, including 44,110 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 0.35 (11395 hom., cov: 33)
  • Exomes 𝑓: 0.25 (32715 hom.)
• Consequence: MMP15 NM_002428.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP15	NM_002428.4	c.748+124A>G		intron_variant		ENST00000219271.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP15	ENST00000219271.4	c.748+124A>G		intron_variant		1	NM_002428.4	P1
MMP15	ENST00000570065.1	c.18+124A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53083 AN: 151992 Hom.: 11348 Cov.: 33

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.251 AC: 235746 AN: 939502 Hom.: 32715 AF XY: 0.247 AC XY: 115621 AN XY: 468830

Gnomad4 AFR exome AF: 0.611

Gnomad4 AMR exome AF: 0.430

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.380

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.350 AC: 53199 AN: 152110 Hom.: 11395 Cov.: 33 AF XY: 0.352 AC XY: 26154 AN XY: 74362

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.285

Alfa AF: 0.229 Hom.: 2315

Bravo AF: 0.369

Asia WGS AF: 0.345 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.13
Dann	Benign	0.30

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: rs2304488; hg19: chr16-58074210;