dbSNP rs28381684: MMP12:c.912-13T>A (chr11-102866461-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002426.6(MMP12):c.912-13T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,608,320 control chromosomes in the GnomAD database, including 11,974 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 0.093 ( 945 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11029 hom. )

Consequence

MMP12
NM_002426.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Variant links:

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]

MMP12 links:

LOC124902741 (HGNC:):

LOC124902741 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP12	NM_002426.6 link	c.912-13T>A		intron_variant	Intron 6 of 9	ENST00000571244.3	NP_002417.2	P39900
LOC124902741	XR_007062868.1 link	n.*62A>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3 link	c.912-13T>A		intron_variant	Intron 6 of 9	1	NM_002426.6	ENSP00000458585.1		P39900

Frequencies

GnomAD3 genomes

AF:

0.0933

AC:

14200

AN:

152118

Hom.:

944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0227

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0711

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.0259

Gnomad SAS

AF:

0.0725

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.0923

GnomAD3 exomes

AF:

0.105

AC:

25293

AN:

241814

Hom.:

1635

AF XY:

0.107

AC XY:

13994

AN XY:

130806

show subpopulations

Gnomad AFR exome

AF:

0.0178

Gnomad AMR exome

AF:

0.0518

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.0252

Gnomad SAS exome

AF:

0.0818

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.118

AC:

172416

AN:

1456084

Hom.:

11029

Cov.:

AF XY:

0.118

AC XY:

85373

AN XY:

723598

show subpopulations

Gnomad4 AFR exome

AF:

0.0178

Gnomad4 AMR exome

AF:

0.0542

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.0258

Gnomad4 SAS exome

AF:

0.0839

Gnomad4 FIN exome

AF:

0.186

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.0933

AC:

14202

AN:

152236

Hom.:

945

Cov.:

AF XY:

0.0948

AC XY:

7053

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0226

Gnomad4 AMR

AF:

0.0710

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.0260

Gnomad4 SAS

AF:

0.0732

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.0903

Alfa

AF:

0.117

Hom.:

224

Bravo

AF:

0.0799

Asia WGS

AF:

0.0540

AC:

189

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.3

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over