Variant rs4756902 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001292063.2(OTOG):c.2561+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,535,456 control chromosomes in the GnomAD database, including 113,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10451 hom., cov: 32)

Exomes 𝑓: 0.38 ( 103338 hom. )

Consequence

OTOG
NM_001292063.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.408

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 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=-0.83).

BP6

Variant 11-17576644-G-A is Benign according to our data. Variant chr11-17576644-G-A is described in ClinVar as [Benign]. Clinvar id is 226871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17576644-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
OTOG	NM_001292063.2 link	c.2561+14G>A		intron_variant		ENST00000399397.6	NP_001278992.1	H9KVB3
OTOG	NM_001277269.2 link	c.2597+14G>A		intron_variant			NP_001264198.1	Q6ZRI0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6 link	c.2561+14G>A		intron_variant		5	NM_001292063.2	ENSP00000382329.2		H9KVB3
OTOG	ENST00000399391.7 link	c.2597+14G>A		intron_variant		5		ENSP00000382323.2		Q6ZRI0-1

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55806

AN:

151632

Hom.:

10443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.376

Gnomad AMI

AF:

0.443

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.360

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.353

GnomAD3 exomes

AF:

0.337

AC:

50288

AN:

149178

Hom.:

8907

AF XY:

0.342

AC XY:

27463

AN XY:

80314

show subpopulations

Gnomad AFR exome

AF:

0.374

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.388

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.314

Gnomad FIN exome

AF:

0.373

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.383

AC:

529857

AN:

1383706

Hom.:

103338

Cov.:

AF XY:

0.382

AC XY:

260795

AN XY:

683272

show subpopulations

Gnomad4 AFR exome

AF:

0.372

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.383

Gnomad4 EAS exome

AF:

0.248

Gnomad4 SAS exome

AF:

0.316

Gnomad4 FIN exome

AF:

0.374

Gnomad4 NFE exome

AF:

0.400

Gnomad4 OTH exome

AF:

0.375

GnomAD4 genome

AF:

0.368

AC:

55840

AN:

151750

Hom.:

10451

Cov.:

AF XY:

0.364

AC XY:

26988

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.377

Gnomad4 AMR

AF:

0.262

Gnomad4 ASJ

AF:

0.381

Gnomad4 EAS

AF:

0.276

Gnomad4 SAS

AF:

0.307

Gnomad4 FIN

AF:

0.373

Gnomad4 NFE

AF:

0.396

Gnomad4 OTH

AF:

0.349

Alfa

AF:

0.378

Hom.:

2231

Bravo

AF:

0.360

Asia WGS

AF:

0.308

AC:

1073

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	2597+14G>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 rs4756902). -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -

Autosomal recessive nonsyndromic hearing loss 18B

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

-0.83

CADD

Benign

2.1

DANN

Benign

0.47

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

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