rs757984

Positions:

• chr11-17598361-T-C
• chr11-17598361-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001292063.2(OTOG):​c.3683-1310T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,234 control chromosomes in the GnomAD database, including 4,137 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4137 hom., cov: 33)
• Consequence: OTOG NM_001292063.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOG	NM_001292063.2	c.3683-1310T>C		intron_variant		ENST00000399397.6
OTOG	NM_001277269.2	c.3719-1310T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOG	ENST00000399397.6	c.3683-1310T>C		intron_variant		5	NM_001292063.2	P2
OTOG	ENST00000399391.7	c.3719-1310T>C		intron_variant		5		A2
OTOG	ENST00000342528.2	n.1047+1354T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34096 AN: 152116 Hom.: 4126 Cov.: 33

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.224 AC: 34129 AN: 152234 Hom.: 4137 Cov.: 33 AF XY: 0.224 AC XY: 16665 AN XY: 74436

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.206

Alfa AF: 0.184 Hom.: 1421

Bravo AF: 0.224

Asia WGS AF: 0.264 AC: 916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.53
DANN	Benign	0.45

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: rs757984; hg19: chr11-17619908;