Variant 15-73927205-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005576.4(LOXL1):c.422G>T(p.Arg141Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,591,266 control chromosomes in the GnomAD database, including 87,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.28 ( 6787 hom., cov: 33)

Exomes 𝑓: 0.33 ( 80552 hom. )

Consequence

LOXL1
NM_005576.4 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 1.83

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013831854).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 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.422G>T	p.Arg141Leu	missense_variant	1/7	ENST00000261921.8	NP_005567.2
LOXL1-AS1	NR_040069.1 linkuse as main transcript	n.184+860C>A		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.422G>T	p.Arg141Leu	missense_variant	1/7	1	NM_005576.4	ENSP00000261921	P1
LOXL1-AS1	ENST00000685373.1 linkuse as main transcript	n.198+572C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43304

AN:

151898

Hom.:

6785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.545

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.175

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.296

GnomAD3 exomes

AF:

0.328

AC:

70580

AN:

215264

Hom.:

12359

AF XY:

0.329

AC XY:

39527

AN XY:

119978

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.307

Gnomad ASJ exome

AF:

0.246

Gnomad EAS exome

AF:

0.543

Gnomad SAS exome

AF:

0.323

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.328

Gnomad OTH exome

AF:

0.334

GnomAD4 exome

AF:

0.330

AC:

475403

AN:

1439260

Hom.:

80552

Cov.:

AF XY:

0.330

AC XY:

236764

AN XY:

716454

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.313

Gnomad4 ASJ exome

AF:

0.256

Gnomad4 EAS exome

AF:

0.544

Gnomad4 SAS exome

AF:

0.323

Gnomad4 FIN exome

AF:

0.307

Gnomad4 NFE exome

AF:

0.332

Gnomad4 OTH exome

AF:

0.318

GnomAD4 genome

AF:

0.285

AC:

43318

AN:

152006

Hom.:

6787

Cov.:

AF XY:

0.288

AC XY:

21386

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.256

Gnomad4 EAS

AF:

0.545

Gnomad4 SAS

AF:

0.330

Gnomad4 FIN

AF:

0.309

Gnomad4 NFE

AF:

0.323

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.276

Hom.:

2108

Bravo

AF:

0.282

TwinsUK

AF:

0.336

AC:

1245

ALSPAC

AF:

0.340

AC:

1311

ESP6500AA

AF:

0.160

AC:

678

ESP6500EA

AF:

0.310

AC:

2569

ExAC

AF:

0.318

AC:

37705

Asia WGS

AF:

0.357

AC:

1239

AN:

3462

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

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

0.58

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.29

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.9

REVEL

Benign

0.080

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.041

Polyphen

0.91

Vest4

0.047

ClinPred

0.016

GERP RS

4.1

Varity_R

0.26

gMVP

0.40

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