rs3825942

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005576.4(LOXL1):c.458G>A(p.Gly153Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,597,506 control chromosomes in the GnomAD database, including 25,880 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (no stars).

Frequency

Genomes: 𝑓 0.22 ( 4501 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21379 hom. )

Consequence

LOXL1
NM_005576.4 missense

Scores

Clinical Significance

Benign; risk factor no assertion criteria provided B:1O:1

Conservation

PhyloP100: 0.949

Publications

185 publications found

Variant links:

Genes affected

LOXL1 (HGNC:6665): (lysyl oxidase like 1) This gene encodes a member of the lysyl oxidase family of proteins. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyzes the first step in the formation of crosslinks in collagen and elastin. The encoded preproprotein is proteolytically processed to generate the mature enzyme. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Mutations in this gene are associated with exfoliation syndrome. [provided by RefSeq, Jan 2016]

LOXL1 links:

LOXL1-AS1 (HGNC:44169): (LOXL1 antisense RNA 1)

LOXL1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014670193).

BP6

Variant 15-73927241-G-A is Benign according to our data. Variant chr15-73927241-G-A is described in ClinVar as Benign|risk_factor. ClinVar VariationId is 14361.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4 link	c.458G>A	p.Gly153Asp	missense_variant	Exon 1 of 7	ENST00000261921.8	NP_005567.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8 link	c.458G>A	p.Gly153Asp	missense_variant	Exon 1 of 7	1	NM_005576.4	ENSP00000261921.7

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33661

AN:

151938

Hom.:

4490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.153

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.201

GnomAD2 exomes

AF:

0.179

AC:

40071

AN:

223790

AF XY:

0.178

show subpopulations

Gnomad AFR exome

AF:

0.397

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.166

AC:

240171

AN:

1445460

Hom.:

21379

Cov.:

AF XY:

0.167

AC XY:

120004

AN XY:

719546

show subpopulations

African (AFR)

AF:

0.387

AC:

12445

AN:

32186

American (AMR)

AF:

0.158

AC:

6970

AN:

43984

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

4366

AN:

25884

East Asian (EAS)

AF:

0.139

AC:

5413

AN:

38968

South Asian (SAS)

AF:

0.219

AC:

18594

AN:

85080

European-Finnish (FIN)

AF:

0.164

AC:

7385

AN:

45050

Middle Eastern (MID)

AF:

0.192

AC:

1101

AN:

5738

European-Non Finnish (NFE)

AF:

0.156

AC:

173302

AN:

1108582

Other (OTH)

AF:

0.177

AC:

10595

AN:

59988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

12365

24729

37094

49458

61823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6284

12568

18852

25136

31420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.222

AC:

33711

AN:

152046

Hom.:

4501

Cov.:

AF XY:

0.220

AC XY:

16346

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.379

AC:

15738

AN:

41482

American (AMR)

AF:

0.153

AC:

2338

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

603

AN:

3468

East Asian (EAS)

AF:

0.123

AC:

632

AN:

5154

South Asian (SAS)

AF:

0.234

AC:

1130

AN:

4822

European-Finnish (FIN)

AF:

0.163

AC:

1729

AN:

10582

Middle Eastern (MID)

AF:

0.147

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.160

AC:

10885

AN:

67942

Other (OTH)

AF:

0.201

AC:

424

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1248

2496

3745

4993

6241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.159

Hom.:

1712

Bravo

AF:

0.227

ESP6500AA

AF:

0.361

AC:

1563

ESP6500EA

AF:

0.145

AC:

1231

ExAC

AF:

0.180

AC:

21647

Asia WGS

AF:

0.197

AC:

683

AN:

3464

ClinVar

Significance: Benign; risk factor

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LOXL1-related disorder

Benign:1

Jun 27, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Exfoliation syndrome, susceptibility to

Other:1

May 01, 2009

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.077

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

PhyloP100

0.95

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.2

REVEL

Benign

0.14

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.040

Polyphen

0.0010

Vest4

0.032

ClinPred

0.018

GERP RS

3.2

Varity_R

0.26

gMVP

0.59

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over