Variant 15-73927261-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005576.4(LOXL1):c.478G>C(p.Ala160Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,601,692 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 14 hom. )

Consequence

LOXL1
NM_005576.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.16

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01631403).

BP6

Variant 15-73927261-G-C is Benign according to our data. Variant chr15-73927261-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2645532.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL1	NM_005576.4 linkuse as main transcript	c.478G>C	p.Ala160Pro	missense_variant	1/7	ENST00000261921.8
LOXL1-AS1	NR_040069.1 linkuse as main transcript	n.184+804C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL1	ENST00000261921.8 linkuse as main transcript	c.478G>C	p.Ala160Pro	missense_variant	1/7	1	NM_005576.4	P1
LOXL1-AS1	ENST00000685373.1 linkuse as main transcript	n.198+516C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

206

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00246

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00122

AC:

278

AN:

227896

Hom.:

AF XY:

0.00122

AC XY:

153

AN XY:

125718

show subpopulations

Gnomad AFR exome

AF:

0.000575

Gnomad AMR exome

AF:

0.000331

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000372

Gnomad FIN exome

AF:

0.000592

Gnomad NFE exome

AF:

0.00225

Gnomad OTH exome

AF:

0.00159

GnomAD4 exome

AF:

0.00248

AC:

3593

AN:

1449428

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

1717

AN XY:

721378

show subpopulations

Gnomad4 AFR exome

AF:

0.000552

Gnomad4 AMR exome

AF:

0.000385

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000539

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00293

Gnomad4 OTH exome

AF:

0.00359

GnomAD4 genome

AF:

0.00135

AC:

206

AN:

152264

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.00246

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00141

ESP6500AA

AF:

0.000917

AC:

ESP6500EA

AF:

0.00305

AC:

ExAC

AF:

0.00122

AC:

147

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

LOXL1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.090

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.95

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.73

REVEL

Benign

0.16

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.055

Polyphen

1.0

Vest4

0.50

MVP

0.60

ClinPred

0.014

GERP RS

4.1

Varity_R

0.38

gMVP

0.56

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