chr11-102872031-G-T

Variant names:

• chr11-102872031-G-T
• rs17368659
• NM_002426.6:c.351-79C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002426.6(MMP12):​c.351-79C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,377,676 control chromosomes in the GnomAD database, including 10,567 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 0.095 (982 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9585 hom.)
• Consequence: MMP12 NM_002426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP12	NM_002426.6	c.351-79C>A		intron_variant	Intron 2 of 9	ENST00000571244.3	NP_002417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.351-79C>A		intron_variant	Intron 2 of 9	1	NM_002426.6	ENSP00000458585.1

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14530 AN: 152104 Hom.: 981 Cov.: 32

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.0800

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.0953

GnomAD4 exome AF: 0.120 AC: 147459 AN: 1225452 Hom.: 9585 AF XY: 0.120 AC XY: 71703 AN XY: 598632

Gnomad4 AFR exome AF: 0.0207 AC: 565 AN: 27306

Gnomad4 AMR exome AF: 0.0594 AC: 1136 AN: 19138

Gnomad4 ASJ exome AF: 0.134 AC: 2490 AN: 18598

Gnomad4 EAS exome AF: 0.0254 AC: 909 AN: 35794

Gnomad4 SAS exome AF: 0.0881 AC: 4958 AN: 56276

Gnomad4 FIN exome AF: 0.190 AC: 8493 AN: 44772

Gnomad4 NFE exome AF: 0.127 AC: 122451 AN: 967274

Gnomad4 Remaining exome AF: 0.112 AC: 5714 AN: 51232

GnomAD4 genome AF: 0.0955 AC: 14532 AN: 152224 Hom.: 982 Cov.: 32 AF XY: 0.0973 AC XY: 7244 AN XY: 74422

Gnomad4 AFR AF: 0.0252 AC: 0.0252022 AN: 0.0252022

Gnomad4 AMR AF: 0.0719 AC: 0.071942 AN: 0.071942

Gnomad4 ASJ AF: 0.120 AC: 0.120242 AN: 0.120242

Gnomad4 EAS AF: 0.0264 AC: 0.0264173 AN: 0.0264173

Gnomad4 SAS AF: 0.0809 AC: 0.0809129 AN: 0.0809129

Gnomad4 FIN AF: 0.214 AC: 0.213611 AN: 0.213611

Gnomad4 NFE AF: 0.130 AC: 0.129959 AN: 0.129959

Gnomad4 OTH AF: 0.0934 AC: 0.0933649 AN: 0.0933649

Alfa AF: 0.116 Hom.: 2214

Bravo AF: 0.0818

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.51

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: rs17368659; hg19: chr11-102742761;