rs626729

Variant names:

• chr11-102862639-T-C
• rs626729
• XR_007062868.1:n.1992-2559T>C

Variant summary

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

The XR_007062868.1(LOC124902741):​n.1992-2559T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,392 control chromosomes in the GnomAD database, including 1,357 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 0.11 (1357 hom., cov: 32)
  • Exomes 𝑓: 0.018 (0 hom.)
• Consequence: LOC124902741 XR_007062868.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

Genes affected

LOC124902741 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124902741	XR_007062868.1	n.1992-2559T>C		intron_variant	Intron 2 of 2
MMP12	NM_002426.6	c.*461A>G		downstream_gene_variant		ENST00000571244.3	NP_002417.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP12	ENST00000571244.3	c.*461A>G		downstream_gene_variant		1	NM_002426.6	ENSP00000458585.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16539 AN: 152166 Hom.: 1353 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0995

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.0182 AC: 2 AN: 110 Hom.: 0 AF XY: 0.0270 AC XY: 2 AN XY: 74

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0114

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.109 AC: 16543 AN: 152282 Hom.: 1357 Cov.: 32 AF XY: 0.107 AC XY: 7933 AN XY: 74472

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.0740

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0983

Gnomad4 FIN AF: 0.0406

Gnomad4 NFE AF: 0.0529

Gnomad4 OTH AF: 0.110

Alfa AF: 0.103 Hom.: 233

Bravo AF: 0.116

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.069
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs626729; hg19: chr11-102733370;