rs4756901

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00100

Publications

9 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 -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 VariationId is 226870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.2561+10G>A		intron_variant	Intron 21 of 55	ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 link	c.2597+10G>A		intron_variant	Intron 20 of 54		NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6 link	c.2561+10G>A		intron_variant	Intron 21 of 55	5	NM_001292063.2	ENSP00000382329.2		H9KVB3
OTOG	ENST00000399391.7 link	c.2597+10G>A		intron_variant	Intron 20 of 54	5		ENSP00000382323.2		Q6ZRI0-1

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50431

AN:

151644

Hom.:

8831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.379

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.324

GnomAD2 exomes

AF:

0.330

AC:

49242

AN:

149210

AF XY:

0.336

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.386

Gnomad EAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.373

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.340

GnomAD4 exome

AF:

0.380

AC:

527086

AN:

1387784

Hom.:

102227

Cov.:

AF XY:

0.379

AC XY:

259558

AN XY:

685080

show subpopulations

African (AFR)

AF:

0.250

AC:

7853

AN:

31422

American (AMR)

AF:

0.197

AC:

7046

AN:

35686

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

9584

AN:

25130

East Asian (EAS)

AF:

0.249

AC:

8868

AN:

35682

South Asian (SAS)

AF:

0.316

AC:

25012

AN:

79068

European-Finnish (FIN)

AF:

0.374

AC:

18012

AN:

48152

Middle Eastern (MID)

AF:

0.339

AC:

1922

AN:

5670

European-Non Finnish (NFE)

AF:

0.400

AC:

427714

AN:

1069308

Other (OTH)

AF:

0.365

AC:

21075

AN:

57666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

13966

27932

41899

55865

69831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13280

26560

39840

53120

66400

<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:

0.332

AC:

50436

AN:

151762

Hom.:

8830

Cov.:

AF XY:

0.329

AC XY:

24425

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.255

AC:

10544

AN:

41422

American (AMR)

AF:

0.246

AC:

3765

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.379

AC:

1312

AN:

3466

East Asian (EAS)

AF:

0.276

AC:

1419

AN:

5146

South Asian (SAS)

AF:

0.306

AC:

1473

AN:

4808

European-Finnish (FIN)

AF:

0.373

AC:

3929

AN:

10534

Middle Eastern (MID)

AF:

0.342

AC:

100

AN:

292

European-Non Finnish (NFE)

AF:

0.395

AC:

26819

AN:

67812

Other (OTH)

AF:

0.320

AC:

675

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1729

3458

5188

6917

8646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.333

Hom.:

3101

Bravo

AF:

0.319

Asia WGS

AF:

0.298

AC:

1039

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

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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). -

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. -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.82

CADD

Benign

(source)

DANN

Benign

0.56

PhyloP100

0.0010

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.22

Position offset: 3

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