rs686375

Variant names:

• chr11-102862503-C-T
• rs686375
• XR_007062868.1:n.1992-2695C>T

Variant summary

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

The XR_007062868.1(LOC124902741):​n.1992-2695C>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 152,164 control chromosomes in the GnomAD database, including 2,329 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 (2329 hom., cov: 32)
• Consequence: LOC124902741 XR_007062868.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000571244.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP12	NM_002426.6	MANE Select	c.*597G>A		downstream_gene	N/A	NP_002417.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP12	ENST00000571244.3	TSL:1 MANE Select	c.*597G>A		downstream_gene	N/A	ENSP00000458585.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20271 AN: 152046 Hom.: 2324 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0818

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: 20285 AN: 152164 Hom.: 2329 Cov.: 32 AF XY: 0.131 AC XY: 9711 AN XY: 74386

African (AFR) AF: 0.313 AC: 12981 AN: 41460

American (AMR) AF: 0.0816 AC: 1248 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3472

East Asian (EAS) AF: 0.110 AC: 568 AN: 5180

South Asian (SAS) AF: 0.0999 AC: 483 AN: 4834

European-Finnish (FIN) AF: 0.0407 AC: 431 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0539 AC: 3667 AN: 68012

Other (OTH) AF: 0.127 AC: 269 AN: 2112

Alfa AF: 0.0873 Hom.: 226

Bravo AF: 0.144

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.71
DANN	Benign	0.50
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs686375; hg19: chr11-102733234;