rs369343034

Positions:

• chr11-17634959-C-G
• chr11-17634959-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001292063.2(OTOG):​c.7585+11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000082 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00057 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OTOG NM_001292063.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTOG	NM_001292063.2	c.7585+11C>G		intron_variant		ENST00000399397.6	NP_001278992.1
OTOG	NM_001277269.2	c.7621+11C>G		intron_variant			NP_001264198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTOG	ENST00000399397.6	c.7585+11C>G		intron_variant		5	NM_001292063.2	ENSP00000382329	P2
OTOG	ENST00000399391.7	c.7621+11C>G		intron_variant		5		ENSP00000382323	A2
OTOG	ENST00000342528.2	n.4606-651C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8 AN: 97112 Hom.: 0 Cov.: 28 FAILED QC

Gnomad AFR AF: 0.000113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000364

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000573 AC: 220 AN: 384236 Hom.: 0 Cov.: 0 AF XY: 0.000508 AC XY: 105 AN XY: 206828

Gnomad4 AFR exome AF: 0.000784

Gnomad4 AMR exome AF: 0.00214

Gnomad4 ASJ exome AF: 0.000397

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000417

Gnomad4 FIN exome AF: 0.000123

Gnomad4 NFE exome AF: 0.000558

Gnomad4 OTH exome AF: 0.000483

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000824 AC: 8 AN: 97140 Hom.: 0 Cov.: 28 AF XY: 0.000105 AC XY: 5 AN XY: 47416

Gnomad4 AFR AF: 0.000113

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000365

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000881

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000565 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs369343034; hg19: chr11-17656506;