Genetic Variant LOXL1:p.Ser161Leu (chr15-73927265-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_005576.4(LOXL1):c.482C>T(p.Ser161Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000433 in 1,601,832 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

LOXL1
NM_005576.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.60

Publications

1 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008223176).

BP6

Variant 15-73927265-C-T is Benign according to our data. Variant chr15-73927265-C-T is described in ClinVar as Benign. ClinVar VariationId is 3040211.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005576.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LOXL1	NM_005576.4	MANE Select	c.482C>T	p.Ser161Leu	missense	Exon 1 of 7	NP_005567.2	Q08397
LOXL1-AS1	NR_040066.1		n.133+389G>A		intron	N/A
LOXL1-AS1	NR_040067.1		n.133+389G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LOXL1	ENST00000261921.8	TSL:1 MANE Select	c.482C>T	p.Ser161Leu	missense	Exon 1 of 7	ENSP00000261921.7	Q08397
LOXL1	ENST00000856631.1		c.482C>T	p.Ser161Leu	missense	Exon 1 of 6	ENSP00000526690.1
LOXL1	ENST00000566011.5	TSL:5	n.482C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000457827.1	H3BUV8

Frequencies

GnomAD3 genomes

AF:

0.00234

AC:

356

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00787

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000641

AC:

146

AN:

227598

AF XY:

0.000494

show subpopulations

Gnomad AFR exome

AF:

0.00838

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000886

GnomAD4 exome

AF:

0.000232

AC:

337

AN:

1449586

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

150

AN XY:

721406

show subpopulations

African (AFR)

AF:

0.00730

AC:

238

AN:

32596

American (AMR)

AF:

0.000974

AC:

AN:

44160

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

25980

East Asian (EAS)

AF:

0.00

AC:

AN:

39198

South Asian (SAS)

AF:

0.0000351

AC:

AN:

85358

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46862

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00000631

AC:

AN:

1109590

Other (OTH)

AF:

0.000749

AC:

AN:

60102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00234

AC:

356

AN:

152246

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00784

AC:

326

AN:

41558

American (AMR)

AF:

0.00163

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67992

Other (OTH)

AF:

0.00142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000146

Hom.:

Bravo

AF:

0.00279

ESP6500AA

AF:

0.00688

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000678

AC:

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

LOXL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

0.13

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0082

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

6.6

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.6

REVEL

Benign

0.096

Sift

Benign

0.25

Sift4G

Benign

0.068

Polyphen

0.78

Vest4

0.40

MVP

0.63

ClinPred

0.054

GERP RS

4.1

Varity_R

0.24

gMVP

0.68

Mutation Taster

=86/14

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over