rs644552

Positions:

• chr11-102864409-G-A

Variant summary

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

The ENST00000571244.3(MMP12):​c.1206-157C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,172 control chromosomes in the GnomAD database, including 2,313 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 0.13 (2313 hom., cov: 32)
• Consequence: MMP12 ENST00000571244.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP12	NM_002426.6	c.1206-157C>T		intron_variant		ENST00000571244.3	NP_002417.2
LOC124902741	XR_007062868.1	n.1992-789G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.1206-157C>T		intron_variant		1	NM_002426.6	ENSP00000458585	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20221 AN: 152054 Hom.: 2308 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0816

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.133 AC: 20235 AN: 152172 Hom.: 2313 Cov.: 32 AF XY: 0.130 AC XY: 9694 AN XY: 74404

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.0813

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0407

Gnomad4 NFE AF: 0.0539

Gnomad4 OTH AF: 0.127

Alfa AF: 0.101 Hom.: 195

Bravo AF: 0.144

Asia WGS AF: 0.118 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.12
DANN	Benign	0.16

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: rs644552; hg19: chr11-102735140; COSMIC: COSV58260855;