rs4756901
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001292063.2(OTOG):c.2561+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,539,546 control chromosomes in the GnomAD database, including 111,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.33 ( 8830 hom., cov: 32)
Exomes 𝑓: 0.38 ( 102227 hom. )
Consequence
OTOG
NM_001292063.2 intron
NM_001292063.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00100
Genes affected
OTOG (HGNC:8516): (otogelin) The protein encoded by this gene is a component of the acellular membranes of the inner ear. Disruption of the orthologous mouse gene shows that it plays a role in auditory and vestibular functions. It is involved in fibrillar network organization, the anchoring of otoconial membranes and cupulae to the neuroepithelia, and likely in sound stimulation resistance. Mutations in this gene cause autosomal recessive nonsyndromic deafness, type 18B. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 11-17576640-G-A is Benign according to our data. Variant chr11-17576640-G-A is described in ClinVar as [Benign]. Clinvar id is 226870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17576640-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.2561+10G>A | intron_variant | ENST00000399397.6 | |||
OTOG | NM_001277269.2 | c.2597+10G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.2561+10G>A | intron_variant | 5 | NM_001292063.2 | P2 | |||
OTOG | ENST00000399391.7 | c.2597+10G>A | intron_variant | 5 | A2 |
Frequencies
GnomAD3 genomes AF: 0.333 AC: 50431AN: 151644Hom.: 8831 Cov.: 32
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GnomAD3 exomes AF: 0.330 AC: 49242AN: 149210Hom.: 8568 AF XY: 0.336 AC XY: 27013AN XY: 80334
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GnomAD4 exome AF: 0.380 AC: 527086AN: 1387784Hom.: 102227 Cov.: 32 AF XY: 0.379 AC XY: 259558AN XY: 685080
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GnomAD4 genome AF: 0.332 AC: 50436AN: 151762Hom.: 8830 Cov.: 32 AF XY: 0.329 AC XY: 24425AN XY: 74164
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | 2597+10G>A in intron 20 of OTOG: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence. It has been identified in 43.3% (77/178) of English and Scottish chromosom es from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih. gov/projects/SNP; dbSNP rs4756901). - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | 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. - |
Autosomal recessive nonsyndromic hearing loss 18B Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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Splicing
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Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at