18-46524695-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_001384474.1(LOXHD1):c.4740+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,399,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000050 ( 0 hom. )
Consequence
LOXHD1
NM_001384474.1 intron
NM_001384474.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.414
Publications
0 publications found
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]
LOXHD1 Gene-Disease associations (from GenCC):
- autosomal recessive nonsyndromic hearing loss 77Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
- nonsyndromic genetic hearing lossInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Fuchs' endothelial dystrophyInheritance: AD Classification: LIMITED Submitted by: Illumina
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 18-46524695-C-T is Benign according to our data. Variant chr18-46524695-C-T is described in CliVar as Likely_benign. Clinvar id is 2980619.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-46524695-C-T is described in CliVar as Likely_benign. Clinvar id is 2980619.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-46524695-C-T is described in CliVar as Likely_benign. Clinvar id is 2980619.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-46524695-C-T is described in CliVar as Likely_benign. Clinvar id is 2980619.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-46524695-C-T is described in CliVar as Likely_benign. Clinvar id is 2980619.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-46524695-C-T is described in CliVar as Likely_benign. Clinvar id is 2980619.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-46524695-C-T is described in CliVar as Likely_benign. Clinvar id is 2980619.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-46524695-C-T is described in CliVar as Likely_benign. Clinvar id is 2980619.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-46524695-C-T is described in CliVar as Likely_benign. Clinvar id is 2980619.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-46524695-C-T is described in CliVar as Likely_benign. Clinvar id is 2980619.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.4740+13G>A | intron_variant | Intron 30 of 40 | ENST00000642948.1 | NP_001371403.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.4740+13G>A | intron_variant | Intron 30 of 40 | NM_001384474.1 | ENSP00000496347.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000500 AC: 7AN: 1399376Hom.: 0 Cov.: 32 AF XY: 0.00000580 AC XY: 4AN XY: 690202 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
1399376
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
690202
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31598
American (AMR)
AF:
AC:
0
AN:
35704
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25182
East Asian (EAS)
AF:
AC:
1
AN:
35738
South Asian (SAS)
AF:
AC:
0
AN:
79236
European-Finnish (FIN)
AF:
AC:
0
AN:
49256
Middle Eastern (MID)
AF:
AC:
0
AN:
5698
European-Non Finnish (NFE)
AF:
AC:
6
AN:
1078966
Other (OTH)
AF:
AC:
0
AN:
57998
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.482
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Dec 22, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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