rs545542156

Variant names:

• chr11-17635201-A-T
• rs545542156
• NM_001292063.2:c.7693+14A>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001292063.2(OTOG):​c.7693+14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,528,748 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (9 hom.)
• Consequence: OTOG NM_001292063.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.47

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=-0.88).
• BP6: Variant 11-17635201-A-T is Benign according to our data. Variant chr11-17635201-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 227798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00197 (299/151436) while in subpopulation NFE AF= 0.00303 (205/67752). AF 95% confidence interval is 0.00269. There are 1 homozygotes in gnomad4. There are 153 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTOG	NM_001292063.2	c.7693+14A>T		intron_variant	Intron 46 of 55	ENST00000399397.6	NP_001278992.1
OTOG	NM_001277269.2	c.7729+14A>T		intron_variant	Intron 45 of 54		NP_001264198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6	c.7693+14A>T		intron_variant	Intron 46 of 55	5	NM_001292063.2	ENSP00000382329.2
OTOG	ENST00000399391.7	c.7729+14A>T		intron_variant	Intron 45 of 54	5		ENSP00000382323.2
OTOG	ENST00000342528.2	n.4606-409A>T		intron_variant	Intron 19 of 21	2

Frequencies

GnomAD3 genomes AF: 0.00198 AC: 299 AN: 151318 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000778

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00332

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00166 AC: 219 AN: 132164 Hom.: 1 AF XY: 0.00159 AC XY: 114 AN XY: 71878

Gnomad AFR exome AF: 0.000315

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.000901

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000456

Gnomad FIN exome AF: 0.00317

Gnomad NFE exome AF: 0.00297

Gnomad OTH exome AF: 0.00101

GnomAD4 exome AF: 0.00268 AC: 3698 AN: 1377312 Hom.: 9 Cov.: 31 AF XY: 0.00268 AC XY: 1822 AN XY: 679546

Gnomad4 AFR exome AF: 0.000416

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.000806

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000114

Gnomad4 FIN exome AF: 0.00365

Gnomad4 NFE exome AF: 0.00315

Gnomad4 OTH exome AF: 0.00148

GnomAD4 genome AF: 0.00197 AC: 299 AN: 151436 Hom.: 1 Cov.: 32 AF XY: 0.00207 AC XY: 153 AN XY: 73972

Gnomad4 AFR AF: 0.000776

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00332

Gnomad4 NFE AF: 0.00303

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00201 Hom.: 0

Bravo AF: 0.00180

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Aug 21, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.7729+14A>T in intron 45 of OTOG: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. It has been identified in 0.4% (3/686) of Finnish chromosomes and in 0.1% (3/3450) of European (non-Finnish) chromosomes by the Exome Aggregation Consortium (ExAC , http://exac.broadinstitute.org; dbSNP rs545542156). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.014
DANN	Benign	0.42

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: rs545542156; hg19: chr11-17656748;