Variant 15-73927258-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005576.4(LOXL1):c.475T>G(p.Ser159Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00821 in 1,601,216 control chromosomes in the GnomAD database, including 913 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.045 ( 509 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 404 hom. )

Consequence

LOXL1
NM_005576.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.985

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=0.0016031265).

BP6

Variant 15-73927258-T-G is Benign according to our data. Variant chr15-73927258-T-G is described in ClinVar as [Benign]. Clinvar id is 3055709.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4 link	c.475T>G	p.Ser159Ala	missense_variant	Exon 1 of 7	ENST00000261921.8	NP_005567.2	Q08397

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8 link	c.475T>G	p.Ser159Ala	missense_variant	Exon 1 of 7	1	NM_005576.4	ENSP00000261921.7		Q08397

Frequencies

GnomAD3 genomes

AF:

0.0451

AC:

6861

AN:

152084

Hom.:

508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000530

Gnomad OTH

AF:

0.0325

GnomAD3 exomes

AF:

0.0106

AC:

2413

AN:

227168

Hom.:

175

AF XY:

0.00763

AC XY:

956

AN XY:

125364

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.00676

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000443

Gnomad OTH exome

AF:

0.00355

GnomAD4 exome

AF:

0.00433

AC:

6269

AN:

1449024

Hom.:

404

Cov.:

AF XY:

0.00365

AC XY:

2632

AN XY:

721184

show subpopulations

Gnomad4 AFR exome

AF:

0.153

Gnomad4 AMR exome

AF:

0.00845

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000398

Gnomad4 FIN exome

AF:

0.0000431

Gnomad4 NFE exome

AF:

0.000239

Gnomad4 OTH exome

AF:

0.00963

GnomAD4 genome

AF:

0.0451

AC:

6870

AN:

152192

Hom.:

509

Cov.:

AF XY:

0.0431

AC XY:

3209

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.158

Gnomad4 AMR

AF:

0.0142

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.0322

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0513

ESP6500AA

AF:

0.143

AC:

620

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0136

AC:

1642

Asia WGS

AF:

0.00785

AC:

AN:

3454

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LOXL1-related disorder

Benign:1

Jan 24, 2020

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.70

REVEL

Benign

0.015

Sift

Benign

0.46

Sift4G

Benign

0.28

Polyphen

0.18

Vest4

0.090

ClinPred

0.0040

GERP RS

2.9

Varity_R

0.071

gMVP

0.57

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