rs3825942

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000261921.8(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. 11/19 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
ENST00000261921.8 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.949

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
LOXL1	NM_005576.4 linkuse as main transcript	c.458G>A	p.Gly153Asp	missense_variant	1/7	ENST00000261921.8	NP_005567.2
LOXL1-AS1	NR_040069.1 linkuse as main transcript	n.184+824C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8 linkuse as main transcript	c.458G>A	p.Gly153Asp	missense_variant	1/7	1	NM_005576.4	ENSP00000261921	P1
LOXL1-AS1	ENST00000685373.1 linkuse as main transcript	n.198+536C>T		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes

AF:

0.179

AC:

40071

AN:

223790

Hom.:

4120

AF XY:

0.178

AC XY:

22000

AN XY:

123772

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 SAS exome

AF:

0.217

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

Gnomad4 AFR exome

AF:

0.387

Gnomad4 AMR exome

AF:

0.158

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.219

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.156

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.222

AC:

33711

AN:

152046

Hom.:

4501

Cov.:

AF XY:

0.220

AC XY:

16346

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.379

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.174

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.163

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.201

Alfa

AF:

0.153

Hom.:

1395

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 27, 2019

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

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2009

- -

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

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

MutationTaster

Benign

0.012

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over