chr11-102871238-A-G

Variant names:

• chr11-102871238-A-G
• rs7123600
• NM_002426.6:c.625+356T>C

Variant summary

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

The NM_002426.6(MMP12):​c.625+356T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,910 control chromosomes in the GnomAD database, including 6,149 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 0.27 (6149 hom., cov: 31)
• Consequence: MMP12 NM_002426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 9 publications found

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP12	NM_002426.6	c.625+356T>C		intron_variant	Intron 4 of 9	ENST00000571244.3	NP_002417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.625+356T>C		intron_variant	Intron 4 of 9	1	NM_002426.6	ENSP00000458585.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41634 AN: 151792 Hom.: 6146 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.274 AC: 41643 AN: 151910 Hom.: 6149 Cov.: 31 AF XY: 0.275 AC XY: 20377 AN XY: 74224

African (AFR) AF: 0.156 AC: 6456 AN: 41404

American (AMR) AF: 0.271 AC: 4141 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 848 AN: 3466

East Asian (EAS) AF: 0.244 AC: 1259 AN: 5166

South Asian (SAS) AF: 0.461 AC: 2213 AN: 4800

European-Finnish (FIN) AF: 0.294 AC: 3107 AN: 10552

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22634 AN: 67932

Other (OTH) AF: 0.277 AC: 587 AN: 2116

Alfa AF: 0.282 Hom.: 1034

Bravo AF: 0.264

Asia WGS AF: 0.354 AC: 1231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.42
PhyloP100		1.4

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

Other links and lift over

dbSNP: rs7123600; hg19: chr11-102741968;