rs28381684

Variant names:

• chr11-102866461-A-T
• rs28381684
• NM_002426.6:c.912-13T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 16 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: Benign. The variant received -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	c.912-13T>A		intron_variant	Intron 6 of 9	ENST00000571244.3	NP_002417.2
LOC124902741	XR_007062868.1	n.*62A>T		downstream_gene_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14200 AN: 152118 Hom.: 944 Cov.: 32

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

GnomAD2 exomes AF: 0.105 AC: 25293 AN: 241814 AF XY: 0.107

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 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.: 31 AF XY: 0.118 AC XY: 85373 AN XY: 723598

African (AFR) AF: 0.0178 AC: 595 AN: 33362

American (AMR) AF: 0.0542 AC: 2394 AN: 44168

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3134 AN: 26036

East Asian (EAS) AF: 0.0258 AC: 1023 AN: 39598

South Asian (SAS) AF: 0.0839 AC: 7102 AN: 84606

European-Finnish (FIN) AF: 0.186 AC: 9880 AN: 53238

Middle Eastern (MID) AF: 0.128 AC: 739 AN: 5762

European-Non Finnish (NFE) AF: 0.127 AC: 140937 AN: 1109122

Other (OTH) AF: 0.110 AC: 6612 AN: 60192

GnomAD4 genome AF: 0.0933 AC: 14202 AN: 152236 Hom.: 945 Cov.: 32 AF XY: 0.0948 AC XY: 7053 AN XY: 74420

African (AFR) AF: 0.0226 AC: 940 AN: 41576

American (AMR) AF: 0.0710 AC: 1086 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3466

East Asian (EAS) AF: 0.0260 AC: 135 AN: 5192

South Asian (SAS) AF: 0.0732 AC: 353 AN: 4822

European-Finnish (FIN) AF: 0.207 AC: 2188 AN: 10584

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8788 AN: 67988

Other (OTH) AF: 0.0903 AC: 191 AN: 2114

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
PhyloP100		2.0

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

Other links and lift over

dbSNP: rs28381684; hg19: chr11-102737192;