rs2041028

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001292063.2(OTOG):c.4904C>T(p.Pro1635Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,550,170 control chromosomes in the GnomAD database, including 115,879 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15276 hom., cov: 32)

Exomes 𝑓: 0.37 ( 100603 hom. )

Consequence

OTOG
NM_001292063.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.102

Publications

18 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), 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.881634E-6).

BP6

Variant 11-17610204-C-T is Benign according to our data. Variant chr11-17610204-C-T is described in ClinVar as Benign. ClinVar VariationId is 226895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292063.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	NM_001292063.2	MANE Select	c.4904C>T	p.Pro1635Leu	missense	Exon 36 of 56	NP_001278992.1	H9KVB3
	OTOG	NM_001277269.2		c.4940C>T	p.Pro1647Leu	missense	Exon 35 of 55	NP_001264198.1	Q6ZRI0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OTOG	ENST00000399397.6	TSL:5 MANE Select	c.4904C>T	p.Pro1635Leu	missense	Exon 36 of 56	ENSP00000382329.2	H9KVB3
OTOG	ENST00000399391.7	TSL:5	c.4940C>T	p.Pro1647Leu	missense	Exon 35 of 55	ENSP00000382323.2	Q6ZRI0-1
OTOG	ENST00000342528.2	TSL:2	n.2242C>T		non_coding_transcript_exon	Exon 12 of 22

Frequencies

GnomAD3 genomes

AF:

0.429

AC:

65198

AN:

151866

Hom.:

15251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.624

Gnomad AMI

AF:

0.441

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.391

GnomAD2 exomes

AF:

0.353

AC:

52585

AN:

149160

AF XY:

0.360

show subpopulations

Gnomad AFR exome

AF:

0.635

Gnomad AMR exome

AF:

0.221

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.340

Gnomad NFE exome

AF:

0.372

Gnomad OTH exome

AF:

0.333

GnomAD4 exome

AF:

0.374

AC:

522758

AN:

1398186

Hom.:

100603

Cov.:

AF XY:

0.375

AC XY:

258806

AN XY:

689618

show subpopulations

African (AFR)

AF:

0.631

AC:

19948

AN:

31598

American (AMR)

AF:

0.233

AC:

8306

AN:

35694

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

8511

AN:

25164

East Asian (EAS)

AF:

0.194

AC:

6919

AN:

35732

South Asian (SAS)

AF:

0.444

AC:

35150

AN:

79226

European-Finnish (FIN)

AF:

0.337

AC:

16239

AN:

48190

Middle Eastern (MID)

AF:

0.350

AC:

1992

AN:

5698

European-Non Finnish (NFE)

AF:

0.375

AC:

404101

AN:

1078882

Other (OTH)

AF:

0.372

AC:

21592

AN:

58002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

20747

41493

62240

82986

103733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13030

26060

39090

52120

65150

<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:

0.429

AC:

65264

AN:

151984

Hom.:

15276

Cov.:

AF XY:

0.426

AC XY:

31631

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.624

AC:

25872

AN:

41438

American (AMR)

AF:

0.314

AC:

4791

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

1147

AN:

3472

East Asian (EAS)

AF:

0.202

AC:

1045

AN:

5166

South Asian (SAS)

AF:

0.460

AC:

2214

AN:

4808

European-Finnish (FIN)

AF:

0.333

AC:

3522

AN:

10588

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.373

AC:

25344

AN:

67922

Other (OTH)

AF:

0.391

AC:

824

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1797

3594

5391

7188

8985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.388

Hom.:

27038

Bravo

AF:

0.428

TwinsUK

AF:

0.376

AC:

1396

ALSPAC

AF:

0.365

AC:

1407

ExAC

AF:

0.313

AC:

8096

Asia WGS

AF:

0.372

AC:

1294

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.0

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.017

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0000089

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.4

PhyloP100

0.10

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.040

REVEL

Benign

0.059

Sift

Benign

0.59

Sift4G

Benign

0.44

Vest4

0.076

ClinPred

0.0053

GERP RS

4.1

Varity_R

0.025

gMVP

0.20

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over