rs28363645

chr22-23779101-G-A

Variant summary

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

The NM_005940.5(MMP11):c.109-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,092,624 control chromosomes in the GnomAD database, including 813 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 0.035 (140 hom., cov: 33)
  • Exomes 𝑓: 0.034 (673 hom.)
• Consequence: MMP11 NM_005940.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65

Genes affected

MMP11 (HGNC:7157): (matrix metallopeptidase 11) 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. However, the enzyme encoded by this gene is activated intracellularly by furin within the constitutive secretory pathway. Also in contrast to other MMP's, this enzyme cleaves alpha 1-proteinase inhibitor but weakly degrades structural proteins of the extracellular matrix. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP11	NM_005940.5	c.109-86G>A		intron_variant		ENST00000215743.8
MMP11	NR_133013.2	n.131-86G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP11	ENST00000215743.8	c.109-86G>A		intron_variant		1	NM_005940.5	P1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5266 AN: 152188 Hom.: 138 Cov.: 33

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0455

GnomAD4 exome AF: 0.0343 AC: 32207 AN: 940318 Hom.: 673 AF XY: 0.0346 AC XY: 16216 AN XY: 468512

Gnomad4 AFR exome AF: 0.0338

Gnomad4 AMR exome AF: 0.0180

Gnomad4 ASJ exome AF: 0.0481

Gnomad4 EAS exome AF: 0.0874

Gnomad4 SAS exome AF: 0.0437

Gnomad4 FIN exome AF: 0.0247

Gnomad4 NFE exome AF: 0.0308

Gnomad4 OTH exome AF: 0.0418

GnomAD4 genome AF: 0.0346 AC: 5272 AN: 152306 Hom.: 140 Cov.: 33 AF XY: 0.0351 AC XY: 2613 AN XY: 74474

Gnomad4 AFR AF: 0.0342

Gnomad4 AMR AF: 0.0207

Gnomad4 ASJ AF: 0.0524

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.0466

Gnomad4 FIN AF: 0.0220

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.0374 Hom.: 14

Bravo AF: 0.0346

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.0050
Dann	Benign	0.36

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: rs28363645; hg19: chr22-24121288;