18-46593590-C-A
Variant summary
Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001384474.1(LOXHD1):c.1431+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,552,124 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001384474.1 intron
Scores
Clinical Significance
Conservation
Publications
- 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
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ACMG classification
Our verdict: Benign. The variant received -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.1431+10G>T | intron_variant | Intron 10 of 40 | ENST00000642948.1 | NP_001371403.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.1431+10G>T | intron_variant | Intron 10 of 40 | NM_001384474.1 | ENSP00000496347.1 | ||||
LOXHD1 | ENST00000536736.5 | c.1431+10G>T | intron_variant | Intron 10 of 39 | 5 | ENSP00000444586.1 | ||||
LOXHD1 | ENST00000441551.6 | c.1431+10G>T | intron_variant | Intron 10 of 38 | 5 | ENSP00000387621.2 | ||||
LOXHD1 | ENST00000335730.6 | n.744+10G>T | intron_variant | Intron 3 of 26 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00605 AC: 921AN: 152206Hom.: 6 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00139 AC: 224AN: 160682 AF XY: 0.000963 show subpopulations
GnomAD4 exome AF: 0.000609 AC: 853AN: 1399800Hom.: 13 Cov.: 31 AF XY: 0.000550 AC XY: 380AN XY: 690332 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00604 AC: 920AN: 152324Hom.: 6 Cov.: 32 AF XY: 0.00571 AC XY: 425AN XY: 74476 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 77 Uncertain:1Benign:1
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not provided Benign:2
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not specified Benign:1
1431+10G>T in Intron 10 of LOXHD1: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence and has been identified in 1.4% (10/702) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs57330753). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at