11-17638557-C-T

Position:

chr11-17638557-C-T

Variant summary

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

The NM_001292063.2(OTOG):c.7894+8C>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 0.0401 in 1,549,324 control chromosomes in the GnomAD database, including 1,437 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 0.040 ( 139 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1298 hom. )

Consequence

OTOG
NM_001292063.2 splice_region, intron

Scores

Splicing: ADA: 0.00004638

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.27

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=-0.67).

BP6

Variant 11-17638557-C-T is Benign according to our data. Variant chr11-17638557-C-T is described in ClinVar as [Benign]. Clinvar id is 226912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOG	NM_001292063.2 linkuse as main transcript	c.7894+8C>T		splice_region_variant, intron_variant		ENST00000399397.6	NP_001278992.1
OTOG	NM_001277269.2 linkuse as main transcript	c.7930+8C>T		splice_region_variant, intron_variant			NP_001264198.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6 linkuse as main transcript	c.7894+8C>T	splice_region_variant, intron_variant	5	NM_001292063.2	ENSP00000382329	P2
OTOG	ENST00000399391.7 linkuse as main transcript	c.7930+8C>T	splice_region_variant, intron_variant	5		ENSP00000382323	A2	Q6ZRI0-1
OTOG	ENST00000342528.2 linkuse as main transcript	n.4806+8C>T	splice_region_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0397

AC:

6041

AN:

152078

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0401

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0523

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.0531

Gnomad SAS

AF:

0.0869

Gnomad FIN

AF:

0.0349

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0346

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0442

AC:

6542

AN:

147882

Hom.:

215

AF XY:

0.0462

AC XY:

3682

AN XY:

79654

show subpopulations

Gnomad AFR exome

AF:

0.0368

Gnomad AMR exome

AF:

0.0437

Gnomad ASJ exome

AF:

0.0264

Gnomad EAS exome

AF:

0.0540

Gnomad SAS exome

AF:

0.0848

Gnomad FIN exome

AF:

0.0332

Gnomad NFE exome

AF:

0.0334

Gnomad OTH exome

AF:

0.0365

GnomAD4 exome

AF:

0.0401

AC:

56050

AN:

1397126

Hom.:

1298

Cov.:

AF XY:

0.0413

AC XY:

28459

AN XY:

689126

show subpopulations

Gnomad4 AFR exome

AF:

0.0394

Gnomad4 AMR exome

AF:

0.0424

Gnomad4 ASJ exome

AF:

0.0256

Gnomad4 EAS exome

AF:

0.0432

Gnomad4 SAS exome

AF:

0.0828

Gnomad4 FIN exome

AF:

0.0311

Gnomad4 NFE exome

AF:

0.0379

Gnomad4 OTH exome

AF:

0.0365

GnomAD4 genome

AF:

0.0398

AC:

6051

AN:

152198

Hom.:

139

Cov.:

AF XY:

0.0418

AC XY:

3107

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0400

Gnomad4 AMR

AF:

0.0525

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.0530

Gnomad4 SAS

AF:

0.0871

Gnomad4 FIN

AF:

0.0349

Gnomad4 NFE

AF:

0.0346

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0349

Hom.:

Bravo

AF:

0.0377

Asia WGS

AF:

0.0850

AC:

295

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	7930+8C>T in intron 47 of OTOG: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 7.2% (14/194) of Luhya (Kenyan) chromosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.gov/proj ects/SNP; dbSNP rs11024353). -
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. -

not provided

Benign:2

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	- -

OTOG-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 29, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.2

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000046

dbscSNV1_RF

Benign

0.0

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