rs215901

Positions:

chr16-21719128-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_144672.4(OTOA):c.1630-5C>T variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00009088

Clinical Significance

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

Conservation

PhyloP100: 0.457

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 47952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-21719128-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
OTOA	NM_144672.4 linkuse as main transcript	c.1630-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000646100.2	NP_653273.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOA	ENST00000646100.2 linkuse as main transcript	c.1630-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_144672.4	ENSP00000496564	P2	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

GnomAD3 exomes

AF:

0.625

AC:

156782

AN:

250836

Hom.:

49814

AF XY:

0.636

AC XY:

86180

AN XY:

135558

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 SAS exome

AF:

0.663

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

Gnomad4 AFR exome

AF:

0.582

Gnomad4 AMR exome

AF:

0.498

Gnomad4 ASJ exome

AF:

0.649

Gnomad4 EAS exome

AF:

0.525

Gnomad4 SAS exome

AF:

0.668

Gnomad4 FIN exome

AF:

0.642

Gnomad4 NFE exome

AF:

0.671

Gnomad4 OTH exome

AF:

0.644

GnomAD4 genome

AF:

0.628

AC:

95490

AN:

152030

Hom.:

30277

Cov.:

AF XY:

0.625

AC XY:

46485

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.580

Gnomad4 AMR

AF:

0.566

Gnomad4 ASJ

AF:

0.645

Gnomad4 EAS

AF:

0.509

Gnomad4 SAS

AF:

0.668

Gnomad4 FIN

AF:

0.636

Gnomad4 NFE

AF:

0.675

Gnomad4 OTH

AF:

0.636

Alfa

AF:

0.666

Hom.:

54334

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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	May 07, 2012	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). -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive nonsyndromic hearing loss 22

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.56

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

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