chr11-102864299-C-T

Variant names:

• chr11-102864299-C-T
• rs476391
• NM_002426.6:c.1206-47G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002426.6(MMP12):​c.1206-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000851 in 1,175,268 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: MMP12 NM_002426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• Publications: 0 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]

LOC124902741 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP12	NM_002426.6	c.1206-47G>A		intron_variant	Intron 8 of 9	ENST00000571244.3	NP_002417.2
LOC124902741	XR_007062868.1	n.1992-899C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.1206-47G>A		intron_variant	Intron 8 of 9	1	NM_002426.6	ENSP00000458585.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.51e-7 AC: 1 AN: 1175268 Hom.: 0 Cov.: 16 AF XY: 0.00000168 AC XY: 1 AN XY: 596980

African (AFR) AF: 0.00 AC: 0 AN: 28142

American (AMR) AF: 0.00 AC: 0 AN: 41988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24218

East Asian (EAS) AF: 0.00 AC: 0 AN: 38082

South Asian (SAS) AF: 0.00 AC: 0 AN: 78916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5252

European-Non Finnish (NFE) AF: 0.00000117 AC: 1 AN: 854996

Other (OTH) AF: 0.00 AC: 0 AN: 51016

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.30
PhyloP100		-0.41

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: rs476391; hg19: chr11-102735030;