chr11-17594181-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001292063.2(OTOG):c.3408+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,550,434 control chromosomes in the GnomAD database, including 20,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1684 hom., cov: 33)

Exomes 𝑓: 0.16 ( 18511 hom. )

Consequence

OTOG
NM_001292063.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.542

Variant links:

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]

OTOG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-17594181-C-T is Benign according to our data. Variant chr11-17594181-C-T is described in ClinVar as [Benign]. Clinvar id is 226886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17594181-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.3408+15C>T		intron_variant	Intron 28 of 55	ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 link	c.3444+15C>T		intron_variant	Intron 27 of 54		NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
OTOG	ENST00000399397.6 link	c.3408+15C>T	intron_variant	Intron 28 of 55	5	NM_001292063.2	ENSP00000382329.2	H9KVB3
OTOG	ENST00000399391.7 link	c.3444+15C>T	intron_variant	Intron 27 of 54	5		ENSP00000382323.2	Q6ZRI0-1
OTOG	ENST00000342528.2 link	n.773+15C>T	intron_variant	Intron 5 of 21	2

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21559

AN:

152128

Hom.:

1685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.102

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.147

GnomAD3 exomes

AF:

0.152

AC:

22707

AN:

149136

Hom.:

1912

AF XY:

0.157

AC XY:

12626

AN XY:

80328

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.0784

Gnomad ASJ exome

AF:

0.186

Gnomad EAS exome

AF:

0.223

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.152

GnomAD4 exome

AF:

0.161

AC:

224663

AN:

1398188

Hom.:

18511

Cov.:

AF XY:

0.162

AC XY:

112027

AN XY:

689628

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.0817

Gnomad4 ASJ exome

AF:

0.184

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.190

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.162

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.142

AC:

21575

AN:

152246

Hom.:

1684

Cov.:

AF XY:

0.141

AC XY:

10520

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.189

Gnomad4 EAS

AF:

0.204

Gnomad4 SAS

AF:

0.199

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.157

Hom.:

552

Bravo

AF:

0.136

Asia WGS

AF:

0.209

AC:

726

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

3444+15C>T in intron 27 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 21.5% (43/200) of Han Chinese chromosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.gov/proje cts/SNP; dbSNP rs7936484). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.1

DANN

Benign

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over