rs2086005
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001384474.1(LOXHD1):c.2175C>T(p.Asn725=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,551,864 control chromosomes in the GnomAD database, including 13,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.091 ( 899 hom., cov: 33)
Exomes 𝑓: 0.13 ( 12301 hom. )
Consequence
LOXHD1
NM_001384474.1 synonymous
NM_001384474.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.452
Genes affected
LOXHD1 (HGNC:26521): (lipoxygenase homology PLAT domains 1) This gene encodes a highly conserved protein consisting entirely of PLAT (polycystin/lipoxygenase/alpha-toxin) domains, thought to be involved in targeting proteins to the plasma membrane. Studies in mice show that this gene is expressed in the mechanosensory hair cells in the inner ear, and mutations in this gene lead to auditory defects, indicating that this gene is essential for normal hair cell function. Screening of human families segregating deafness identified a mutation in this gene which causes DFNB77, a progressive form of autosomal-recessive nonsyndromic hearing loss (ARNSHL). Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 18-46569511-G-A is Benign according to our data. Variant chr18-46569511-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 47926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-46569511-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.452 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.2175C>T | p.Asn725= | synonymous_variant | 16/41 | ENST00000642948.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.2175C>T | p.Asn725= | synonymous_variant | 16/41 | NM_001384474.1 | P1 | ||
LOXHD1 | ENST00000536736.5 | c.2175C>T | p.Asn725= | synonymous_variant | 16/40 | 5 | |||
LOXHD1 | ENST00000441551.6 | c.2175C>T | p.Asn725= | synonymous_variant | 16/39 | 5 | |||
LOXHD1 | ENST00000335730.6 | n.1488C>T | non_coding_transcript_exon_variant | 9/27 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0916 AC: 13938AN: 152194Hom.: 898 Cov.: 33
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GnomAD3 exomes AF: 0.0942 AC: 15082AN: 160144Hom.: 862 AF XY: 0.0947 AC XY: 7953AN XY: 84012
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GnomAD4 exome AF: 0.127 AC: 177356AN: 1399552Hom.: 12301 Cov.: 32 AF XY: 0.125 AC XY: 86361AN XY: 690282
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GnomAD4 genome ? AF: 0.0915 AC: 13935AN: 152312Hom.: 899 Cov.: 33 AF XY: 0.0858 AC XY: 6391AN XY: 74474
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Asn725Asn in Exon 16 of LOXHD1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 16.2% (411/2532) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2086005). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Autosomal recessive nonsyndromic hearing loss 77 Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at