rs17368582

Positions:

• chr11-102867344-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002426.6(MMP12):​c.837A>G​(p.Pro279Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,610,294 control chromosomes in the GnomAD database, including 11,624 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 0.090 (904 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10720 hom.)
• Consequence: MMP12 NM_002426.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

Genes affected

MMP12 (HGNC:7158): (matrix metallopeptidase 12) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this 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. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease degrades soluble and insoluble elastin. This gene may play a role in aneurysm formation and mutations in this gene are associated with lung function and chronic obstructive pulmonary disease (COPD). This gene is part of a cluster of MMP genes on chromosome 11. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=0.057 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP12	NM_002426.6	c.837A>G	p.Pro279Pro	synonymous_variant	6/10	ENST00000571244.3	NP_002417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.837A>G	p.Pro279Pro	synonymous_variant	6/10	1	NM_002426.6	ENSP00000458585.1

Frequencies

GnomAD3 genomes AF: 0.0905 AC: 13771 AN: 152122 Hom.: 904 Cov.: 32

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0701

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.0903

GnomAD3 exomes AF: 0.0987 AC: 24176 AN: 244894 Hom.: 1547 AF XY: 0.101 AC XY: 13353 AN XY: 132612

Gnomad AFR exome AF: 0.0176

Gnomad AMR exome AF: 0.0518

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.000619

Gnomad SAS exome AF: 0.0574

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.110

GnomAD4 exome AF: 0.115 AC: 168342 AN: 1458054 Hom.: 10720 Cov.: 31 AF XY: 0.114 AC XY: 82981 AN XY: 724970

Gnomad4 AFR exome AF: 0.0176

Gnomad4 AMR exome AF: 0.0539

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.000379

Gnomad4 SAS exome AF: 0.0603

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0905 AC: 13771 AN: 152240 Hom.: 904 Cov.: 32 AF XY: 0.0910 AC XY: 6775 AN XY: 74432

Gnomad4 AFR AF: 0.0224

Gnomad4 AMR AF: 0.0700

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.0884

Alfa AF: 0.118 Hom.: 1985

Bravo AF: 0.0783

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.8
DANN	Benign	0.54

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: rs17368582; hg19: chr11-102738075;