16-58040306-A-G

Variant names:

• chr16-58040306-A-G
• rs2304488
• NM_002428.4:c.748+124A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002428.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP15	NM_002428.4	MANE Select	c.748+124A>G		intron	N/A	NP_002419.1	P51511

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP15	ENST00000219271.4	TSL:1 MANE Select	c.748+124A>G		intron	N/A	ENSP00000219271.3	P51511
	MMP15	ENST00000930621.1		c.748+124A>G		intron	N/A	ENSP00000600680.1
	MMP15	ENST00000907594.1		c.748+124A>G		intron	N/A	ENSP00000577653.1

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

African (AFR) AF: 0.611 AC: 13350 AN: 21860

American (AMR) AF: 0.430 AC: 9826 AN: 22836

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 2275 AN: 17330

East Asian (EAS) AF: 0.380 AC: 12722 AN: 33464

South Asian (SAS) AF: 0.214 AC: 12236 AN: 57288

European-Finnish (FIN) AF: 0.317 AC: 9690 AN: 30540

Middle Eastern (MID) AF: 0.130 AC: 481 AN: 3686

European-Non Finnish (NFE) AF: 0.231 AC: 164372 AN: 710418

Other (OTH) AF: 0.257 AC: 10794 AN: 42080

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

African (AFR) AF: 0.597 AC: 24774 AN: 41492

American (AMR) AF: 0.367 AC: 5613 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3472

East Asian (EAS) AF: 0.371 AC: 1908 AN: 5146

South Asian (SAS) AF: 0.221 AC: 1064 AN: 4824

European-Finnish (FIN) AF: 0.319 AC: 3384 AN: 10594

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15171 AN: 67982

Other (OTH) AF: 0.285 AC: 602 AN: 2112

Alfa AF: 0.234 Hom.: 2708

Bravo AF: 0.369

Asia WGS AF: 0.345 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.13
DANN	Benign	0.30
PhyloP100		-1.5
PromoterAI		0.016	Neutral
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: rs2304488; hg19: chr16-58074210;