rs7936484

chr11-17594181-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001292063.2(OTOG):c.3408+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,550,434 control chromosomes in the GnomAD database, including 20,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1684 hom., cov: 33)
  • Exomes 𝑓: 0.16 (18511 hom.)
• Consequence: OTOG NM_001292063.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.542

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-17594181-C-T is Benign according to our data. Variant chr11-17594181-C-T is described in ClinVar as [Benign]. Clinvar id is 226886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17594181-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOG	NM_001292063.2	c.3408+15C>T		intron_variant		ENST00000399397.6
OTOG	NM_001277269.2	c.3444+15C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOG	ENST00000399397.6	c.3408+15C>T		intron_variant		5	NM_001292063.2	P2
OTOG	ENST00000399391.7	c.3444+15C>T		intron_variant		5		A2
OTOG	ENST00000342528.2	n.773+15C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21559 AN: 152128 Hom.: 1685 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.147

GnomAD3 exomes AF: 0.152 AC: 22707 AN: 149136 Hom.: 1912 AF XY: 0.157 AC XY: 12626 AN XY: 80328

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.0784

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.223

Gnomad SAS exome AF: 0.191

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.161 AC: 224663 AN: 1398188 Hom.: 18511 Cov.: 33 AF XY: 0.162 AC XY: 112027 AN XY: 689628

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0817

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.142 AC: 21575 AN: 152246 Hom.: 1684 Cov.: 33 AF XY: 0.141 AC XY: 10520 AN XY: 74438

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.146

Alfa AF: 0.157 Hom.: 552

Bravo AF: 0.136

Asia WGS AF: 0.209 AC: 726 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	3444+15C>T in intron 27 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 21.5% (43/200) of Han Chinese chromosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.gov/proje cts/SNP; dbSNP rs7936484). -
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	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.1
Dann	Benign	0.39

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

Other links and lift over

dbSNP: rs7936484; hg19: chr11-17615728; COSMIC: COSV61133544;