rs78803776

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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

Publications

6 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=0.0016031265).

BP6

Variant 15-73927258-T-G is Benign according to our data. Variant chr15-73927258-T-G is described in ClinVar as Benign. ClinVar VariationId 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

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

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

GnomAD2 exomes

AF:

0.0106

AC:

2413

AN:

227168

AF XY:

0.00763

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 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

African (AFR)

AF:

0.153

AC:

4967

AN:

32534

American (AMR)

AF:

0.00845

AC:

373

AN:

44150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25978

East Asian (EAS)

AF:

0.00

AC:

AN:

39170

South Asian (SAS)

AF:

0.000398

AC:

AN:

85360

European-Finnish (FIN)

AF:

0.0000431

AC:

AN:

46436

Middle Eastern (MID)

AF:

0.00853

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.000239

AC:

265

AN:

1109558

Other (OTH)

AF:

0.00963

AC:

579

AN:

60094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

326

652

979

1305

1631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<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:

0.0451

AC:

6870

AN:

152192

Hom.:

509

Cov.:

AF XY:

0.0431

AC XY:

3209

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.158

AC:

6543

AN:

41532

American (AMR)

AF:

0.0142

AC:

218

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000515

AC:

AN:

67978

Other (OTH)

AF:

0.0322

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

319

638

956

1275

1594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0188

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

(source)

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

PhyloP100

0.98

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

Mutation Taster

=96/4

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