rs476391

Positions:

• chr11-102864299-C-G

Variant summary

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

The NM_002426.6(MMP12):​c.1206-47G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0638 in 1,326,854 control chromosomes in the GnomAD database, including 3,667 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 0.096 (959 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2708 hom.)
• Consequence: MMP12 NM_002426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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]

LOC124902741 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP12	NM_002426.6	c.1206-47G>C		intron_variant		ENST00000571244.3	NP_002417.2
LOC124902741	XR_007062868.1	n.1992-899C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.1206-47G>C		intron_variant		1	NM_002426.6	ENSP00000458585.1

Frequencies

GnomAD3 genomes AF: 0.0962 AC: 14618 AN: 151948 Hom.: 954 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0689

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0937

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0974

GnomAD3 exomes AF: 0.0714 AC: 16205 AN: 226940 Hom.: 803 AF XY: 0.0712 AC XY: 8714 AN XY: 122430

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.0416

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.128

Gnomad SAS exome AF: 0.0922

Gnomad FIN exome AF: 0.0405

Gnomad NFE exome AF: 0.0503

Gnomad OTH exome AF: 0.0734

GnomAD4 exome AF: 0.0596 AC: 70017 AN: 1174788 Hom.: 2708 Cov.: 16 AF XY: 0.0606 AC XY: 36180 AN XY: 596722

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.0438

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.0837

Gnomad4 SAS exome AF: 0.0920

Gnomad4 FIN exome AF: 0.0420

Gnomad4 NFE exome AF: 0.0496

Gnomad4 OTH exome AF: 0.0784

GnomAD4 genome AF: 0.0962 AC: 14624 AN: 152066 Hom.: 959 Cov.: 32 AF XY: 0.0945 AC XY: 7024 AN XY: 74342

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.0687

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.0926

Gnomad4 FIN AF: 0.0406

Gnomad4 NFE AF: 0.0527

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0803 Hom.: 109

Bravo AF: 0.102

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.45

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: rs476391; hg19: chr11-102735030; COSMIC: COSV58259978;