rs7199221

Variant names:

• chr16-3051638-G-A
• rs7199221
• NM_022468.5:c.661+1092G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-3051638-G-A
• chr16-3051638-G-C
• chr16-3051638-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+1092G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,904 control chromosomes in the GnomAD database, including 8,709 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 0.33 (8707 hom., cov: 31)
  • Exomes 𝑓: 0.23 (2 hom.)
• Consequence: MMP25 NM_022468.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP25	NM_022468.5	c.661+1092G>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+1092G>A		intron_variant	Intron 4 of 9	1	NM_022468.5	ENSP00000337816.4

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49845 AN: 151756 Hom.: 8679 Cov.: 31

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.233 AC: 7 AN: 30 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 6 AN XY: 24

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.329 AC: 49928 AN: 151874 Hom.: 8707 Cov.: 31 AF XY: 0.331 AC XY: 24557 AN XY: 74190

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.315

Alfa AF: 0.276 Hom.: 6914

Bravo AF: 0.322

Asia WGS AF: 0.235 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.0
DANN	Benign	0.41

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: rs7199221; hg19: chr16-3101639;