11-102865688-T-C

Position:

• chr11-102865688-T-C

Variant summary

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

The NM_002426.6(MMP12):​c.1205+88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 1,104,076 control chromosomes in the GnomAD database, including 3,618 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 0.11 (1355 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2263 hom.)
• Consequence: MMP12 NM_002426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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]

LOC124902741 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP12	NM_002426.6	c.1205+88A>G		intron_variant		ENST00000571244.3	NP_002417.2
LOC124902741	XR_007062868.1	n.2482T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.1205+88A>G		intron_variant		1	NM_002426.6	ENSP00000458585	P1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16514 AN: 152006 Hom.: 1350 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.0575 AC: 54747 AN: 951952 Hom.: 2263 AF XY: 0.0584 AC XY: 27730 AN XY: 474556

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.0525

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.0797

Gnomad4 SAS exome AF: 0.0923

Gnomad4 FIN exome AF: 0.0416

Gnomad4 NFE exome AF: 0.0466

Gnomad4 OTH exome AF: 0.0788

GnomAD4 genome AF: 0.109 AC: 16520 AN: 152124 Hom.: 1355 Cov.: 32 AF XY: 0.107 AC XY: 7925 AN XY: 74390

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.0740

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0985

Gnomad4 FIN AF: 0.0406

Gnomad4 NFE AF: 0.0528

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0588 Hom.: 399

Bravo AF: 0.116

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.37

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: rs651159; hg19: chr11-102736419; COSMIC: COSV58261420;