rs4757548

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001292063.2(OTOG):c.2340G>A(p.Pro780Pro) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P780P) has been classified as Likely 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:5

Conservation

PhyloP100: -0.372

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 18B
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine, Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

OTOG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 226868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.2340G>A	p.Pro780Pro	synonymous_variant	Exon 20 of 56	ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 link	c.2376G>A	p.Pro792Pro	synonymous_variant	Exon 19 of 55		NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6 link	c.2340G>A	p.Pro780Pro	synonymous_variant	Exon 20 of 56	5	NM_001292063.2	ENSP00000382329.2		H9KVB3
OTOG	ENST00000399391.7 link	c.2376G>A	p.Pro792Pro	synonymous_variant	Exon 19 of 55	5		ENSP00000382323.2		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

GnomAD2 exomes

AF:

0.337

AC:

50313

AN:

149100

AF XY:

0.342

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 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

African (AFR)

AF:

0.369

AC:

11648

AN:

31580

American (AMR)

AF:

0.208

AC:

7404

AN:

35666

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

9663

AN:

25156

East Asian (EAS)

AF:

0.228

AC:

8136

AN:

35718

South Asian (SAS)

AF:

0.316

AC:

25059

AN:

79196

European-Finnish (FIN)

AF:

0.378

AC:

18242

AN:

48226

Middle Eastern (MID)

AF:

0.352

AC:

2004

AN:

5696

European-Non Finnish (NFE)

AF:

0.404

AC:

436354

AN:

1078838

Other (OTH)

AF:

0.378

AC:

21896

AN:

57984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

18695

37389

56084

74778

93473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13628

27256

40884

54512

68140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.370

AC:

56224

AN:

152158

Hom.:

10621

Cov.:

AF XY:

0.366

AC XY:

27196

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.375

AC:

15555

AN:

41520

American (AMR)

AF:

0.265

AC:

4050

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

1322

AN:

3468

East Asian (EAS)

AF:

0.266

AC:

1376

AN:

5172

South Asian (SAS)

AF:

0.309

AC:

1492

AN:

4828

European-Finnish (FIN)

AF:

0.378

AC:

4006

AN:

10586

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.400

AC:

27167

AN:

67970

Other (OTH)

AF:

0.349

AC:

735

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1819

3638

5457

7276

9095

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.391

Hom.:

21905

Bravo

AF:

0.360

Asia WGS

AF:

0.307

AC:

1068

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

May 09, 2017

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. -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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). -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 18B

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.3

(source)

DANN

Benign

0.53

PhyloP100

-0.37

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over