rs28381684

chr11-102866461-A-T

Variant summary

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

The NM_002426.6(MMP12):c.912-13T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,608,320 control chromosomes in the GnomAD database, including 11,974 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 0.093 (945 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11029 hom.)
• Consequence: MMP12 NM_002426.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

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=-0.81).
• 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	UniProt
MMP12	NM_002426.6	c.912-13T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000571244.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP12	ENST00000571244.3	c.912-13T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002426.6	P1

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14200 AN: 152118 Hom.: 944 Cov.: 32

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0259

Gnomad SAS AF: 0.0725

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.0923

GnomAD3 exomes AF: 0.105 AC: 25293 AN: 241814 Hom.: 1635 AF XY: 0.107 AC XY: 13994 AN XY: 130806

Gnomad AFR exome AF: 0.0178

Gnomad AMR exome AF: 0.0518

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.0252

Gnomad SAS exome AF: 0.0818

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.118 AC: 172416 AN: 1456084 Hom.: 11029 Cov.: 31 AF XY: 0.118 AC XY: 85373 AN XY: 723598

Gnomad4 AFR exome AF: 0.0178

Gnomad4 AMR exome AF: 0.0542

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.0258

Gnomad4 SAS exome AF: 0.0839

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.0933 AC: 14202 AN: 152236 Hom.: 945 Cov.: 32 AF XY: 0.0948 AC XY: 7053 AN XY: 74420

Gnomad4 AFR AF: 0.0226

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0260

Gnomad4 SAS AF: 0.0732

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.117 Hom.: 224

Bravo AF: 0.0799

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.3
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs28381684; hg19: chr11-102737192;