rs662028

Positions:

• chr11-102869898-A-G

Variant summary

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

The NM_002426.6(MMP12):​c.625+1696T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,190 control chromosomes in the GnomAD database, including 1,886 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 0.12 (1886 hom., cov: 32)
• Consequence: MMP12 NM_002426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP12	NM_002426.6	c.625+1696T>C		intron_variant		ENST00000571244.3	NP_002417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.625+1696T>C		intron_variant		1	NM_002426.6	ENSP00000458585.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18632 AN: 152074 Hom.: 1876 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.114

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18665 AN: 152190 Hom.: 1886 Cov.: 32 AF XY: 0.120 AC XY: 8961 AN XY: 74426

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.0776

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.0945

Gnomad4 FIN AF: 0.0407

Gnomad4 NFE AF: 0.0530

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0948 Hom.: 155

Bravo AF: 0.132

Asia WGS AF: 0.114 AC: 396 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	1.6
DANN	Benign	0.55

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: rs662028; hg19: chr11-102740628;