rs1467251

Variant names:

• chr8-88259833-G-A
• rs1467251
• NM_005941.5:c.133-62527C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005941.5(MMP16):​c.133-62527C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,078 control chromosomes in the GnomAD database, including 4,127 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 0.22 (4127 hom., cov: 32)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410
• Publications: 5 publications found

Genes affected

MMP16 (HGNC:7162): (matrix metallopeptidase 16) Proteins of the matrix metalloproteinase (MMP) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The encoded protein activates MMP2 by cleavage. This gene was once referred to as MT-MMP2, but was renamed as MT-MMP3 or MMP16. [provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP16	NM_005941.5	c.133-62527C>T		intron_variant	Intron 1 of 9	ENST00000286614.11	NP_005932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP16	ENST00000286614.11	c.133-62527C>T		intron_variant	Intron 1 of 9	1	NM_005941.5	ENSP00000286614.6
MMP16	ENST00000544227.5	n.133-62527C>T		intron_variant	Intron 1 of 7	1
MMP16	ENST00000522726.1	c.184-62527C>T		intron_variant	Intron 2 of 4	4		ENSP00000429147.1
MMP16	ENST00000520568.1	n.183-62527C>T		intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32844 AN: 151960 Hom.: 4110 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32887 AN: 152078 Hom.: 4127 Cov.: 32 AF XY: 0.212 AC XY: 15730 AN XY: 74352

African (AFR) AF: 0.343 AC: 14199 AN: 41442

American (AMR) AF: 0.146 AC: 2228 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 821 AN: 3472

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5178

South Asian (SAS) AF: 0.152 AC: 732 AN: 4824

European-Finnish (FIN) AF: 0.152 AC: 1609 AN: 10592

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12413 AN: 67974

Other (OTH) AF: 0.220 AC: 464 AN: 2110

Alfa AF: 0.189 Hom.: 12646

Bravo AF: 0.219

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.52
DANN	Benign	0.44
PhyloP100		-0.41
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: rs1467251; hg19: chr8-89272062;