dbSNP rs626729: LOC124902741:n.1992-2559T>C (chr11-102862639-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.93

Publications

8 publications found

Variant links:

Genes affected

LOC124902741 (HGNC:):

LOC124902741 links:

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	n.1992-2559T>C		intron_variant	Intron 2 of 2
MMP12	NM_002426.6 link	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 link	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.:

show subpopulations

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:

AN:

110

Hom.:

AF XY:

0.0270

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0114

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.109

AC:

16543

AN:

152282

Hom.:

1357

Cov.:

AF XY:

0.107

AC XY:

7933

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.229

AC:

9511

AN:

41528

American (AMR)

AF:

0.0740

AC:

1132

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

443

AN:

3470

East Asian (EAS)

AF:

0.110

AC:

570

AN:

5186

South Asian (SAS)

AF:

0.0983

AC:

475

AN:

4832

European-Finnish (FIN)

AF:

0.0406

AC:

431

AN:

10622

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0529

AC:

3596

AN:

68032

Other (OTH)

AF:

0.110

AC:

233

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

732

1465

2197

2930

3662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.55

PhyloP100

-1.9

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over