chr8-88063751-T-C

Variant names:

• chr8-88063751-T-C
• rs1824717
• NM_005941.5:c.1223-7473A>G

Variant summary

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

The NM_005941.5(MMP16):​c.1223-7473A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,782 control chromosomes in the GnomAD database, including 20,774 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 0.52 (20774 hom., cov: 31)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005941.5. 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
	MMP16	NM_005941.5	MANE Select	c.1223-7473A>G		intron	N/A	NP_005932.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP16	ENST00000286614.11	TSL:1 MANE Select	c.1223-7473A>G		intron	N/A	ENSP00000286614.6

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78708 AN: 151664 Hom.: 20755 Cov.: 31

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.519 AC: 78764 AN: 151782 Hom.: 20774 Cov.: 31 AF XY: 0.522 AC XY: 38728 AN XY: 74174

African (AFR) AF: 0.462 AC: 19110 AN: 41378

American (AMR) AF: 0.626 AC: 9526 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2001 AN: 3470

East Asian (EAS) AF: 0.705 AC: 3602 AN: 5110

South Asian (SAS) AF: 0.570 AC: 2748 AN: 4822

European-Finnish (FIN) AF: 0.494 AC: 5214 AN: 10562

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34696 AN: 67904

Other (OTH) AF: 0.539 AC: 1135 AN: 2104

Alfa AF: 0.502 Hom.: 12484

Bravo AF: 0.527

Asia WGS AF: 0.640 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.79
PhyloP100		-0.051
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: rs1824717; hg19: chr8-89075979;