rs7936484

Variant names:

• chr11-17594181-C-T
• rs7936484
• NM_001292063.2:c.3408+15C>T

Variant summary

Our verdict is Benign. The variant received -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:6
• Conservation: PhyloP100: -0.542
• Publications: 8 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), 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=-0.82).
• BP6: Variant 11-17594181-C-T is Benign according to our data. Variant chr11-17594181-C-T is described in ClinVar as Benign. ClinVar VariationId is 226886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	NM_001292063.2	MANE Select	c.3408+15C>T		intron	N/A	NP_001278992.1	H9KVB3
	OTOG	NM_001277269.2		c.3444+15C>T		intron	N/A	NP_001264198.1	Q6ZRI0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTOG	ENST00000399397.6	TSL:5 MANE Select	c.3408+15C>T		intron	N/A	ENSP00000382329.2	H9KVB3
	OTOG	ENST00000399391.7	TSL:5	c.3444+15C>T		intron	N/A	ENSP00000382323.2	Q6ZRI0-1
	OTOG	ENST00000342528.2	TSL:2	n.773+15C>T		intron	N/A

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

GnomAD2 exomes AF: 0.152 AC: 22707 AN: 149136 AF XY: 0.157

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 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

African (AFR) AF: 0.107 AC: 3386 AN: 31594

American (AMR) AF: 0.0817 AC: 2918 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4623 AN: 25178

East Asian (EAS) AF: 0.191 AC: 6827 AN: 35730

South Asian (SAS) AF: 0.190 AC: 15048 AN: 79232

European-Finnish (FIN) AF: 0.132 AC: 6350 AN: 48164

Middle Eastern (MID) AF: 0.157 AC: 897 AN: 5698

European-Non Finnish (NFE) AF: 0.162 AC: 175126 AN: 1078898

Other (OTH) AF: 0.164 AC: 9488 AN: 57990

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

African (AFR) AF: 0.105 AC: 4341 AN: 41540

American (AMR) AF: 0.101 AC: 1551 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 654 AN: 3468

East Asian (EAS) AF: 0.204 AC: 1057 AN: 5184

South Asian (SAS) AF: 0.199 AC: 959 AN: 4818

European-Finnish (FIN) AF: 0.127 AC: 1348 AN: 10608

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11007 AN: 68004

Other (OTH) AF: 0.146 AC: 309 AN: 2112

Alfa AF: 0.157 Hom.: 555

Bravo AF: 0.136

Asia WGS AF: 0.209 AC: 726 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.39
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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