rs1064875

Variant names:

• chr16-3052208-G-A
• rs1064875
• NM_022468.5:c.661+1662G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-3052208-G-A
• chr16-3052208-G-C
• chr16-3052208-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MMP25	NM_022468.5	c.661+1662G>A		intron_variant	Intron 4 of 9	ENST00000336577.9	NP_071913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP25	ENST00000336577.9	c.661+1662G>A		intron_variant	Intron 4 of 9	1	NM_022468.5	ENSP00000337816.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 6 AN: 48

Other (OTH) AF: 0.125 AC: 1 AN: 8

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

African (AFR) AF: 0.232 AC: 9565 AN: 41296

American (AMR) AF: 0.247 AC: 3755 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3468

East Asian (EAS) AF: 0.191 AC: 983 AN: 5154

South Asian (SAS) AF: 0.196 AC: 943 AN: 4804

European-Finnish (FIN) AF: 0.170 AC: 1796 AN: 10546

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.205 AC: 13927 AN: 67936

Other (OTH) AF: 0.192 AC: 404 AN: 2106

Alfa AF: 0.208 Hom.: 7414

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
PhyloP100		-0.0090
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: rs1064875; hg19: chr16-3102209;