chr18-46529181-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001384474.1(LOXHD1):c.4526G>A(p.Gly1509Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0063 in 1,551,526 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1509R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001384474.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.4526G>A | p.Gly1509Glu | missense_variant | 29/41 | ENST00000642948.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.4526G>A | p.Gly1509Glu | missense_variant | 29/41 | NM_001384474.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00698 AC: 1061AN: 152016Hom.: 19 Cov.: 32
GnomAD3 exomes AF: 0.00783 AC: 1242AN: 158560Hom.: 27 AF XY: 0.00735 AC XY: 614AN XY: 83516
GnomAD4 exome AF: 0.00622 AC: 8711AN: 1399392Hom.: 88 Cov.: 32 AF XY: 0.00609 AC XY: 4202AN XY: 690196
GnomAD4 genome AF: 0.00697 AC: 1061AN: 152134Hom.: 19 Cov.: 32 AF XY: 0.00867 AC XY: 645AN XY: 74354
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 77 Uncertain:1Benign:3
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 08, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Mar 16, 2017 | - - |
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | LOXHD1: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Mar 17, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 26, 2018 | 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. - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 07, 2016 | p.Gly1509Glu in exon 29 of LOXHD1: This variant is not expected to have clinical significance because it has been identified in 5% (80/1614) of Finnish chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs187587197). - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 12, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at