chr15-73927215-C-T
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_005576.4(LOXL1):c.432C>T(p.Thr144=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,595,310 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0013 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 2 hom. )
Consequence
LOXL1
NM_005576.4 synonymous
NM_005576.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00400
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 15-73927215-C-T is Benign according to our data. Variant chr15-73927215-C-T is described in ClinVar as [Benign]. Clinvar id is 707936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.004 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LOXL1 | NM_005576.4 | c.432C>T | p.Thr144= | synonymous_variant | 1/7 | ENST00000261921.8 | NP_005567.2 | |
LOXL1-AS1 | NR_040069.1 | n.184+850G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LOXL1 | ENST00000261921.8 | c.432C>T | p.Thr144= | synonymous_variant | 1/7 | 1 | NM_005576.4 | ENSP00000261921 | P1 | |
LOXL1-AS1 | ENST00000685373.1 | n.198+562G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00131 AC: 199AN: 152156Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.000223 AC: 49AN: 220180Hom.: 0 AF XY: 0.000147 AC XY: 18AN XY: 122254
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GnomAD4 exome AF: 0.000142 AC: 205AN: 1443046Hom.: 2 Cov.: 35 AF XY: 0.000121 AC XY: 87AN XY: 718374
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GnomAD4 genome AF: 0.00131 AC: 200AN: 152264Hom.: 2 Cov.: 33 AF XY: 0.00111 AC XY: 83AN XY: 74448
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 28, 2018 | - - |
LOXL1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 12, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at