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rs3825942

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005576.4(LOXL1):c.458G>A(p.Gly153Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,597,506 control chromosomes in the GnomAD database, including 25,880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 4501 hom., cov: 33)
Exomes 𝑓: 0.17 ( 21379 hom. )

Consequence

LOXL1
NM_005576.4 missense

Scores

2
3
13

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 0.949
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-AS1 (HGNC:44169): (LOXL1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0014670193).
BP6
Variant 15-73927241-G-A is Benign according to our data. Variant chr15-73927241-G-A is described in ClinVar as [Benign]. Clinvar id is 14361.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LOXL1NM_005576.4 linkuse as main transcriptc.458G>A p.Gly153Asp missense_variant 1/7 ENST00000261921.8
LOXL1-AS1NR_040069.1 linkuse as main transcriptn.184+824C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LOXL1ENST00000261921.8 linkuse as main transcriptc.458G>A p.Gly153Asp missense_variant 1/71 NM_005576.4 P1
LOXL1-AS1ENST00000685373.1 linkuse as main transcriptn.198+536C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.222
AC:
33661
AN:
151938
Hom.:
4490
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.379
Gnomad AMI
AF:
0.209
Gnomad AMR
AF:
0.153
Gnomad ASJ
AF:
0.174
Gnomad EAS
AF:
0.123
Gnomad SAS
AF:
0.234
Gnomad FIN
AF:
0.163
Gnomad MID
AF:
0.153
Gnomad NFE
AF:
0.160
Gnomad OTH
AF:
0.201
GnomAD3 exomes
AF:
0.179
AC:
40071
AN:
223790
Hom.:
4120
AF XY:
0.178
AC XY:
22000
AN XY:
123772
show subpopulations
Gnomad AFR exome
AF:
0.397
Gnomad AMR exome
AF:
0.160
Gnomad ASJ exome
AF:
0.172
Gnomad EAS exome
AF:
0.119
Gnomad SAS exome
AF:
0.217
Gnomad FIN exome
AF:
0.170
Gnomad NFE exome
AF:
0.158
Gnomad OTH exome
AF:
0.171
GnomAD4 exome
AF:
0.166
AC:
240171
AN:
1445460
Hom.:
21379
Cov.:
40
AF XY:
0.167
AC XY:
120004
AN XY:
719546
show subpopulations
Gnomad4 AFR exome
AF:
0.387
Gnomad4 AMR exome
AF:
0.158
Gnomad4 ASJ exome
AF:
0.169
Gnomad4 EAS exome
AF:
0.139
Gnomad4 SAS exome
AF:
0.219
Gnomad4 FIN exome
AF:
0.164
Gnomad4 NFE exome
AF:
0.156
Gnomad4 OTH exome
AF:
0.177
GnomAD4 genome
AF:
0.222
AC:
33711
AN:
152046
Hom.:
4501
Cov.:
33
AF XY:
0.220
AC XY:
16346
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.379
Gnomad4 AMR
AF:
0.153
Gnomad4 ASJ
AF:
0.174
Gnomad4 EAS
AF:
0.123
Gnomad4 SAS
AF:
0.234
Gnomad4 FIN
AF:
0.163
Gnomad4 NFE
AF:
0.160
Gnomad4 OTH
AF:
0.201
Alfa
AF:
0.153
Hom.:
1395
Bravo
AF:
0.227
ESP6500AA
AF:
0.361
AC:
1563
ESP6500EA
AF:
0.145
AC:
1231
ExAC
AF:
0.180
AC:
21647
Asia WGS
AF:
0.197
AC:
683
AN:
3464

ClinVar

Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

LOXL1-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 27, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Exfoliation syndrome, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMMay 01, 2009- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.66
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.40
Cadd
Benign
22
Dann
Uncertain
1.0
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.077
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.74
T
MetaRNN
Benign
0.0015
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
0.012
P
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.14
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.040
D
Polyphen
0.0010
B
Vest4
0.032
ClinPred
0.018
T
GERP RS
3.2
Varity_R
0.26
gMVP
0.59

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.

Other links and lift over

dbSNP: rs3825942; hg19: chr15-74219582; COSMIC: COSV56093962; COSMIC: COSV56093962; API