rs17368659

Positions:

• chr11-102872031-G-T

Variant summary

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

The NM_002426.6(MMP12):​c.351-79C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,377,676 control chromosomes in the GnomAD database, including 10,567 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 0.095 (982 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9585 hom.)
• Consequence: MMP12 NM_002426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP12	NM_002426.6	c.351-79C>A		intron_variant		ENST00000571244.3	NP_002417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.351-79C>A		intron_variant		1	NM_002426.6	ENSP00000458585	P1

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14530 AN: 152104 Hom.: 981 Cov.: 32

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.0800

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.0953

GnomAD4 exome AF: 0.120 AC: 147459 AN: 1225452 Hom.: 9585 AF XY: 0.120 AC XY: 71703 AN XY: 598632

Gnomad4 AFR exome AF: 0.0207

Gnomad4 AMR exome AF: 0.0594

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.0254

Gnomad4 SAS exome AF: 0.0881

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.0955 AC: 14532 AN: 152224 Hom.: 982 Cov.: 32 AF XY: 0.0973 AC XY: 7244 AN XY: 74422

Gnomad4 AFR AF: 0.0252

Gnomad4 AMR AF: 0.0719

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.0264

Gnomad4 SAS AF: 0.0809

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.0934

Alfa AF: 0.118 Hom.: 561

Bravo AF: 0.0818

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.51

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: rs17368659; hg19: chr11-102742761;