rs1450425
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001384474.1(LOXHD1):c.4530+107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 1,356,964 control chromosomes in the GnomAD database, including 346,192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.66 ( 33931 hom., cov: 29)
Exomes 𝑓: 0.72 ( 312261 hom. )
Consequence
LOXHD1
NM_001384474.1 intron
NM_001384474.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.88
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 18-46529070-T-C is Benign according to our data. Variant chr18-46529070-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 191090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.4530+107A>G | intron_variant | ENST00000642948.1 | NP_001371403.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.4530+107A>G | intron_variant | NM_001384474.1 | ENSP00000496347 | P1 |
Frequencies
GnomAD3 genomes AF: 0.663 AC: 100528AN: 151542Hom.: 33920 Cov.: 29
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GnomAD4 exome AF: 0.718 AC: 865381AN: 1205304Hom.: 312261 AF XY: 0.718 AC XY: 428587AN XY: 596972
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GnomAD4 genome AF: 0.663 AC: 100580AN: 151660Hom.: 33931 Cov.: 29 AF XY: 0.662 AC XY: 49070AN XY: 74086
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 12, 2021 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Sep 28, 2016 | - - |
Autosomal recessive nonsyndromic hearing loss 77 Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
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