rs505770

Variant names:

• chr11-102863479-A-T
• rs505770
• NM_002426.6:c.1313-279T>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.1313-279T>A 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 152,066 control chromosomes in the GnomAD database, including 2,320 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 (2320 hom., cov: 32)
• Consequence: MMP12 NM_002426.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP12	NM_002426.6	c.1313-279T>A		intron_variant	Intron 9 of 9	ENST00000571244.3	NP_002417.2
LOC124902741	XR_007062868.1	n.1992-1719A>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.1313-279T>A		intron_variant	Intron 9 of 9	1	NM_002426.6	ENSP00000458585.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20237 AN: 151948 Hom.: 2315 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0818

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.133 AC: 20251 AN: 152066 Hom.: 2320 Cov.: 32 AF XY: 0.131 AC XY: 9703 AN XY: 74338

African (AFR) AF: 0.313 AC: 12959 AN: 41414

American (AMR) AF: 0.0816 AC: 1247 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3470

East Asian (EAS) AF: 0.109 AC: 565 AN: 5174

South Asian (SAS) AF: 0.0990 AC: 476 AN: 4806

European-Finnish (FIN) AF: 0.0406 AC: 430 AN: 10592

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0539 AC: 3666 AN: 68012

Other (OTH) AF: 0.127 AC: 269 AN: 2110

Alfa AF: 0.103 Hom.: 197

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	-0.92
CADD	Benign	0.62
DANN	Benign	0.82
PhyloP100		-0.062

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: rs505770; hg19: chr11-102734210;