8-88060856-A-G

Variant names:

• chr8-88060856-A-G
• rs1477908
• NM_005941.5:c.1223-4578T>C

Variant summary

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

The NM_005941.5(MMP16):​c.1223-4578T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,890 control chromosomes in the GnomAD database, including 4,676 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 0.23 (4676 hom., cov: 31)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP16	NM_005941.5	MANE Select	c.1223-4578T>C		intron	N/A	NP_005932.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP16	ENST00000286614.11	TSL:1 MANE Select	c.1223-4578T>C		intron	N/A	ENSP00000286614.6

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34682 AN: 151778 Hom.: 4662 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.229 AC: 34715 AN: 151890 Hom.: 4676 Cov.: 31 AF XY: 0.232 AC XY: 17195 AN XY: 74220

African (AFR) AF: 0.278 AC: 11510 AN: 41426

American (AMR) AF: 0.387 AC: 5880 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2159 AN: 5146

South Asian (SAS) AF: 0.220 AC: 1060 AN: 4810

European-Finnish (FIN) AF: 0.146 AC: 1540 AN: 10570

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.160 AC: 10881 AN: 67958

Other (OTH) AF: 0.242 AC: 512 AN: 2112

Alfa AF: 0.188 Hom.: 5046

Bravo AF: 0.254

Asia WGS AF: 0.296 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.55
PhyloP100		0.016
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: rs1477908; hg19: chr8-89073084;