rs10832824

Positions:

chr11-17641897-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001292063.2(OTOG):c.8241C>T(p.Cys2747Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,548,770 control chromosomes in the GnomAD database, including 85,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9863 hom., cov: 31)

Exomes 𝑓: 0.32 ( 75595 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.761

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 11-17641897-C-T is Benign according to our data. Variant chr11-17641897-C-T is described in ClinVar as [Benign]. Clinvar id is 226917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17641897-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.761 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOG	NM_001292063.2 linkuse as main transcript	c.8241C>T	p.Cys2747Cys	synonymous_variant	52/56	ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 linkuse as main transcript	c.8277C>T	p.Cys2759Cys	synonymous_variant	51/55		NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6 linkuse as main transcript	c.8241C>T	p.Cys2747Cys	synonymous_variant	52/56	5	NM_001292063.2	ENSP00000382329.2		H9KVB3
OTOG	ENST00000399391.7 linkuse as main transcript	c.8277C>T	p.Cys2759Cys	synonymous_variant	51/55	5		ENSP00000382323.2		Q6ZRI0-1

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53292

AN:

151756

Hom.:

9852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.474

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.312

GnomAD3 exomes

AF:

0.293

AC:

43350

AN:

148110

Hom.:

6900

AF XY:

0.300

AC XY:

23905

AN XY:

79800

show subpopulations

Gnomad AFR exome

AF:

0.481

Gnomad AMR exome

AF:

0.184

Gnomad ASJ exome

AF:

0.287

Gnomad EAS exome

AF:

0.157

Gnomad SAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.301

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.268

GnomAD4 exome

AF:

0.324

AC:

452835

AN:

1396896

Hom.:

75595

Cov.:

AF XY:

0.325

AC XY:

223629

AN XY:

689050

show subpopulations

Gnomad4 AFR exome

AF:

0.480

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.133

Gnomad4 SAS exome

AF:

0.343

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.332

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.351

AC:

53345

AN:

151874

Hom.:

9863

Cov.:

AF XY:

0.347

AC XY:

25748

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.474

Gnomad4 AMR

AF:

0.258

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.355

Gnomad4 FIN

AF:

0.297

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.312

Alfa

AF:

0.328

Hom.:

6669

Bravo

AF:

0.347

Asia WGS

AF:

0.281

AC:

977

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Cys2759Cys in exon 51 of OTOG: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 51.0% (99/194) of L uhya (Kenyan) chromosomes from a broad population by the 1000 Genomes Project (h ttp://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs10832824). -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive nonsyndromic hearing loss 18B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

May 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.5

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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