rs11225442

Positions:

• chr11-102868589-G-A
• chr11-102868589-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.626-520C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 151,908 control chromosomes in the GnomAD database, including 1,262 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 0.13 (1262 hom., cov: 32)
• Consequence: MMP12 NM_002426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.534

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=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP12	NM_002426.6	c.626-520C>T		intron_variant		ENST00000571244.3	NP_002417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.626-520C>T		intron_variant		1	NM_002426.6	ENSP00000458585.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19348 AN: 151792 Hom.: 1261 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.127 AC: 19357 AN: 151908 Hom.: 1262 Cov.: 32 AF XY: 0.126 AC XY: 9361 AN XY: 74236

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.134

Alfa AF: 0.132 Hom.: 1357

Bravo AF: 0.126

Asia WGS AF: 0.170 AC: 592 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.5
DANN	Benign	0.86

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: rs11225442; hg19: chr11-102739319;