rs4757548

Positions:

chr11-17574766-G-A

Variant summary

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

The NM_001292063.2(OTOG):c.2340G>A(p.Pro780=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,550,218 control chromosomes in the GnomAD database, including 116,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10621 hom., cov: 33)

Exomes 𝑓: 0.39 ( 105942 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.372

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=-0.81).

BP6

Variant 11-17574766-G-A is Benign according to our data. Variant chr11-17574766-G-A is described in ClinVar as [Benign]. Clinvar id is 226868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17574766-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.372 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOG	NM_001292063.2 linkuse as main transcript	c.2340G>A	p.Pro780=	synonymous_variant	20/56	ENST00000399397.6
OTOG	NM_001277269.2 linkuse as main transcript	c.2376G>A	p.Pro792=	synonymous_variant	19/55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOG	ENST00000399397.6 linkuse as main transcript	c.2340G>A	p.Pro780=	synonymous_variant	20/56	5	NM_001292063.2	P2
OTOG	ENST00000399391.7 linkuse as main transcript	c.2376G>A	p.Pro792=	synonymous_variant	19/55	5		A2	Q6ZRI0-1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56197

AN:

152040

Hom.:

10617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.352

GnomAD3 exomes

AF:

0.337

AC:

50313

AN:

149100

Hom.:

8975

AF XY:

0.342

AC XY:

27425

AN XY:

80144

show subpopulations

Gnomad AFR exome

AF:

0.369

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.388

Gnomad EAS exome

AF:

0.272

Gnomad SAS exome

AF:

0.314

Gnomad FIN exome

AF:

0.378

Gnomad NFE exome

AF:

0.398

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.387

AC:

540406

AN:

1398060

Hom.:

105942

Cov.:

AF XY:

0.385

AC XY:

265506

AN XY:

689526

show subpopulations

Gnomad4 AFR exome

AF:

0.369

Gnomad4 AMR exome

AF:

0.208

Gnomad4 ASJ exome

AF:

0.384

Gnomad4 EAS exome

AF:

0.228

Gnomad4 SAS exome

AF:

0.316

Gnomad4 FIN exome

AF:

0.378

Gnomad4 NFE exome

AF:

0.404

Gnomad4 OTH exome

AF:

0.378

GnomAD4 genome

AF:

0.370

AC:

56224

AN:

152158

Hom.:

10621

Cov.:

AF XY:

0.366

AC XY:

27196

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.375

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.381

Gnomad4 EAS

AF:

0.266

Gnomad4 SAS

AF:

0.309

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.349

Alfa

AF:

0.390

Hom.:

6415

Bravo

AF:

0.360

Asia WGS

AF:

0.307

AC:

1068

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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	Pro792Pro in exon 19 of OTOG: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 43.3% (77/178) of En glish and Scottish chromosomes from a broad population by the 1000 Genomes Proje ct (http://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs4757548). -

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.3

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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