rs632009

chr11-102867768-C-T

Variant summary

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

The NM_002426.6(MMP12):c.787+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 864,874 control chromosomes in the GnomAD database, including 43,661 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 0.24 (5433 hom., cov: 32)
  • Exomes 𝑓: 0.32 (38228 hom.)
• Consequence: MMP12 NM_002426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP12	NM_002426.6	c.787+140G>A		intron_variant		ENST00000571244.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP12	ENST00000571244.3	c.787+140G>A		intron_variant		1	NM_002426.6	P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36652 AN: 151834 Hom.: 5429 Cov.: 32

Gnomad AFR AF: 0.0673

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0972

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.319 AC: 227303 AN: 712922 Hom.: 38228 AF XY: 0.322 AC XY: 117435 AN XY: 364292

Gnomad4 AFR exome AF: 0.0627

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.398

Gnomad4 FIN exome AF: 0.305

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.290

GnomAD4 genome AF: 0.241 AC: 36651 AN: 151952 Hom.: 5433 Cov.: 32 AF XY: 0.241 AC XY: 17913 AN XY: 74250

Gnomad4 AFR AF: 0.0672

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.0976

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.246

Alfa AF: 0.296 Hom.: 1490

Bravo AF: 0.228

Asia WGS AF: 0.219 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.3
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs632009; hg19: chr11-102738499;