rs1064875

chr16-3052208-G-Achr16-3052208-G-Cchr16-3052208-G-T

Variant summary

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

The NM_022468.5(MMP25):c.661+1662G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,798 control chromosomes in the GnomAD database, including 3,563 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 0.21 (3562 hom., cov: 30)
  • Exomes 𝑓: 0.14 (1 hom.)
• Consequence: MMP25 NM_022468.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

Genes affected

MMP25 (HGNC:14246): (matrix metallopeptidase 25) 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 MMPs are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily, attached to the plasma membrane via a glycosylphosphatidyl inositol anchor. In response to bacterial infection or inflammation, the encoded protein is thought to inactivate alpha-1 proteinase inhibitor, a major tissue protectant against proteolytic enzymes released by activated neutrophils, facilitating the transendothelial migration of neutrophils to inflammatory sites. The encoded protein may also play a role in tumor invasion and metastasis through activation of MMP2. The gene has previously been referred to as MMP20 but has been renamed MMP25. [provided by RefSeq, Jul 2008]

MMP25-AS1 (HGNC:51372): (MMP25 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP25	NM_022468.5	c.661+1662G>A		intron_variant		ENST00000336577.9
MMP25-AS1	NR_123723.1	n.2256C>T		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP25	ENST00000336577.9	c.661+1662G>A		intron_variant		1	NM_022468.5	P1
MMP25-AS1	ENST00000576250.6	n.672-110C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32334 AN: 151618 Hom.: 3556 Cov.: 30

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.194

GnomAD4 exome AF: 0.141 AC: 9 AN: 64 Hom.: 1 Cov.: 0 AF XY: 0.146 AC XY: 7 AN XY: 48

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.213 AC: 32346 AN: 151734 Hom.: 3562 Cov.: 30 AF XY: 0.212 AC XY: 15729 AN XY: 74142

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.192

Alfa AF: 0.207 Hom.: 4893

Bravo AF: 0.222

Asia WGS AF: 0.175 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.57
Dann	Benign	0.50

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: rs1064875; hg19: chr16-3102209;