18-46524695-C-T

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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.414

Publications

0 publications found
Variant links:
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 77
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • nonsyndromic genetic hearing loss
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • hearing loss, autosomal recessive
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • Fuchs' endothelial dystrophy
    Inheritance: 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
LOXHD1NM_001384474.1 linkc.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
LOXHD1ENST00000642948.1 linkc.4740+13G>A intron_variant Intron 30 of 40 NM_001384474.1 ENSP00000496347.1 A0A2R8Y7K4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000500
AC:
7
AN:
1399376
Hom.:
0
Cov.:
32
AF XY:
0.00000580
AC XY:
4
AN XY:
690202
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31598
American (AMR)
AF:
0.00
AC:
0
AN:
35704
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25182
East Asian (EAS)
AF:
0.0000280
AC:
1
AN:
35738
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79236
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49256
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5698
European-Non Finnish (NFE)
AF:
0.00000556
AC:
6
AN:
1078966
Other (OTH)
AF:
0.00
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
75-80
>80
Age
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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.95
DANN
Benign
0.43
PhyloP100
-0.41

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

Other links and lift over

dbSNP: rs570127242; hg19: chr18-44104658; API