rs215901

Variant names:

Variant summary

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

The NM_144672.4(OTOA):c.1630-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 1,611,852 control chromosomes in the GnomAD database, including 347,703 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30277 hom., cov: 32)

Exomes 𝑓: 0.66 ( 317426 hom. )

Consequence

OTOA
NM_144672.4 splice_region, intron

Scores

Splicing: ADA: 0.00009088

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.457

Publications

19 publications found

Variant links:

Genes affected

OTOA (HGNC:16378): (otoancorin) The protein encoded by this gene is specifically expressed in the inner ear, and is located at the interface between the apical surface of the inner ear sensory epithelia and their overlying acellular gels. It is prposed that this protein is involved in the attachment of the inner ear acellular gels to the apical surface of the underlying nonsensory cells. Mutations in this gene are associated with autosomal recessive deafness type 22 (DFNB22). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

OTOA Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 22
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

OTOA 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 (BayesDel_noAF=-0.69).

BP6

Variant 16-21719128-C-T is Benign according to our data. Variant chr16-21719128-C-T is described in ClinVar as Benign. ClinVar VariationId is 47952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOA	NM_144672.4 link	c.1630-5C>T		splice_region_variant, intron_variant	Intron 15 of 28	ENST00000646100.2	NP_653273.3	Q05BM7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOA	ENST00000646100.2 link	c.1630-5C>T		splice_region_variant, intron_variant	Intron 15 of 28		NM_144672.4	ENSP00000496564.2		Q7RTW8-5

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95438

AN:

151912

Hom.:

30259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.580

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.567

Gnomad ASJ

AF:

0.645

Gnomad EAS

AF:

0.510

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.636

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.675

Gnomad OTH

AF:

0.635

GnomAD2 exomes

AF:

0.625

AC:

156782

AN:

250836

AF XY:

0.636

show subpopulations

Gnomad AFR exome

AF:

0.583

Gnomad AMR exome

AF:

0.487

Gnomad ASJ exome

AF:

0.656

Gnomad EAS exome

AF:

0.504

Gnomad FIN exome

AF:

0.637

Gnomad NFE exome

AF:

0.677

Gnomad OTH exome

AF:

0.644

GnomAD4 exome

AF:

0.657

AC:

959542

AN:

1459822

Hom.:

317426

Cov.:

AF XY:

0.659

AC XY:

478791

AN XY:

726286

show subpopulations

African (AFR)

AF:

0.582

AC:

19451

AN:

33434

American (AMR)

AF:

0.498

AC:

22292

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.649

AC:

16961

AN:

26124

East Asian (EAS)

AF:

0.525

AC:

20833

AN:

39694

South Asian (SAS)

AF:

0.668

AC:

57575

AN:

86186

European-Finnish (FIN)

AF:

0.642

AC:

34262

AN:

53406

Middle Eastern (MID)

AF:

0.718

AC:

3911

AN:

5450

European-Non Finnish (NFE)

AF:

0.671

AC:

745433

AN:

1110500

Other (OTH)

AF:

0.644

AC:

38824

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

17728

35457

53185

70914

88642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19164

38328

57492

76656

95820

<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:

0.628

AC:

95490

AN:

152030

Hom.:

30277

Cov.:

AF XY:

0.625

AC XY:

46485

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.580

AC:

24045

AN:

41466

American (AMR)

AF:

0.566

AC:

8642

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.645

AC:

2236

AN:

3468

East Asian (EAS)

AF:

0.509

AC:

2634

AN:

5172

South Asian (SAS)

AF:

0.668

AC:

3226

AN:

4826

European-Finnish (FIN)

AF:

0.636

AC:

6717

AN:

10564

Middle Eastern (MID)

AF:

0.704

AC:

207

AN:

294

European-Non Finnish (NFE)

AF:

0.675

AC:

45862

AN:

67952

Other (OTH)

AF:

0.636

AC:

1344

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1811

3621

5432

7242

9053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.659

Hom.:

70419

Bravo

AF:

0.621

Asia WGS

AF:

0.577

AC:

2010

AN:

3478

EpiCase

AF:

0.676

EpiControl

AF:

0.682

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

1630-5C>T in Intron 14 of OTOA: This variant is not expected to have clinical si gnificance because it has been identified in 40.7% (1520/3738) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs215901). -

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 22

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

-0.69

CADD

Benign

(source)

DANN

Benign

0.56

PhyloP100

0.46

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000091

dbscSNV1_RF

Benign

0.0020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over