chr11-17552085-A-T

Variant names:

• chr11-17552085-A-T
• rs141597314
• NM_001292063.2:c.292+10A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001292063.2(OTOG):​c.292+10A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 1,549,972 control chromosomes in the GnomAD database, including 300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (28 hom., cov: 33)
  • Exomes 𝑓: 0.018 (272 hom.)
• Consequence: OTOG NM_001292063.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.72
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 18B

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine, Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-17552085-A-T is Benign according to our data. Variant chr11-17552085-A-T is described in ClinVar as Benign. ClinVar VariationId is 226881.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 = 0.0144 (2186/152246) while in subpopulation NFE AF = 0.0205 (1395/67986). AF 95% confidence interval is 0.0196. There are 28 homozygotes in GnomAd4. There are 1099 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292063.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	NM_001292063.2	MANE Select	c.292+10A>T		intron	N/A	NP_001278992.1
	OTOG	NM_001277269.2		c.328+10A>T		intron	N/A	NP_001264198.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	ENST00000399397.6	TSL:5 MANE Select	c.292+10A>T		intron	N/A	ENSP00000382329.2
	OTOG	ENST00000399391.7	TSL:5	c.328+10A>T		intron	N/A	ENSP00000382323.2
	OTOG	ENST00000428619.1	TSL:3	c.109+10A>T		intron	N/A	ENSP00000399057.2

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2188 AN: 152128 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.00415

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.0140 AC: 2086 AN: 149136 AF XY: 0.0137

Gnomad AFR exome AF: 0.00308

Gnomad AMR exome AF: 0.00965

Gnomad ASJ exome AF: 0.0188

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0242

Gnomad NFE exome AF: 0.0194

Gnomad OTH exome AF: 0.0165

GnomAD4 exome AF: 0.0184 AC: 25670 AN: 1397726 Hom.: 272 Cov.: 30 AF XY: 0.0180 AC XY: 12408 AN XY: 689452

African (AFR) AF: 0.00301 AC: 95 AN: 31594

American (AMR) AF: 0.0106 AC: 378 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.0191 AC: 482 AN: 25178

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35734

South Asian (SAS) AF: 0.00583 AC: 462 AN: 79230

European-Finnish (FIN) AF: 0.0232 AC: 1118 AN: 48198

Middle Eastern (MID) AF: 0.00878 AC: 50 AN: 5692

European-Non Finnish (NFE) AF: 0.0206 AC: 22250 AN: 1078444

Other (OTH) AF: 0.0144 AC: 833 AN: 57970

GnomAD4 genome AF: 0.0144 AC: 2186 AN: 152246 Hom.: 28 Cov.: 33 AF XY: 0.0148 AC XY: 1099 AN XY: 74452

African (AFR) AF: 0.00414 AC: 172 AN: 41546

American (AMR) AF: 0.0140 AC: 214 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 55 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00519 AC: 25 AN: 4818

European-Finnish (FIN) AF: 0.0271 AC: 288 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0205 AC: 1395 AN: 67986

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0159 Hom.: 6

Bravo AF: 0.0132

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:2

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

328+10A>T in intron 3 of OTOG: This variant is not expected to have clinical sig nificance because it is not located within the conserved splice consensus sequen ce. It has been identified in 4.2% (5/120) of Colombian chromosomes from a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.gov/projects/SN P; dbSNP rs141597314).

Jul 09, 2020

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.3
DANN	Benign	0.68
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs141597314; hg19: chr11-17573632;