rs28363665

Positions:

• chr22-23781540-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.1075+131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 849,898 control chromosomes in the GnomAD database, including 4,508 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 0.12 (2778 hom., cov: 31)
  • Exomes 𝑓: 0.031 (1730 hom.)
• Consequence: MMP11 NM_005940.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP11	NM_005940.5	c.1075+131G>A		intron_variant		ENST00000215743.8	NP_005931.2
MMP11	NR_133013.2	n.1049+131G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP11	ENST00000215743.8	c.1075+131G>A		intron_variant		1	NM_005940.5	ENSP00000215743	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17599 AN: 151920 Hom.: 2765 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0575

Gnomad ASJ AF: 0.0551

Gnomad EAS AF: 0.0257

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0992

GnomAD4 exome AF: 0.0312 AC: 21792 AN: 697860 Hom.: 1730 Cov.: 9 AF XY: 0.0330 AC XY: 11779 AN XY: 357120

Gnomad4 AFR exome AF: 0.374

Gnomad4 AMR exome AF: 0.0438

Gnomad4 ASJ exome AF: 0.0574

Gnomad4 EAS exome AF: 0.0213

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.00355

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.0514

GnomAD4 genome AF: 0.116 AC: 17650 AN: 152038 Hom.: 2778 Cov.: 31 AF XY: 0.113 AC XY: 8420 AN XY: 74350

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.0574

Gnomad4 ASJ AF: 0.0551

Gnomad4 EAS AF: 0.0258

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.0982

Alfa AF: 0.0523 Hom.: 241

Bravo AF: 0.129

Asia WGS AF: 0.0950 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.9
DANN	Benign	0.39

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: rs28363665; hg19: chr22-24123727;