rs7123600

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• 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

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.277

Alfa AF: 0.298 Hom.: 922

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

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: rs7123600; hg19: chr11-102741968;