rs734640

chr11-17591801-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001292063.2(OTOG):c.3006+213A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,054 control chromosomes in the GnomAD database, including 8,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (8952 hom., cov: 32)
• Consequence: OTOG NM_001292063.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.44

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-17591801-A-G is Benign according to our data. Variant chr11-17591801-A-G is described in ClinVar as [Benign]. Clinvar id is 1221300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOG	NM_001292063.2	c.3006+213A>G		intron_variant		ENST00000399397.6
OTOG	NM_001277269.2	c.3042+213A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTOG	ENST00000399397.6	c.3006+213A>G		intron_variant		5	NM_001292063.2	P2
OTOG	ENST00000399391.7	c.3042+213A>G		intron_variant		5		A2
OTOG	ENST00000342528.2	n.372-1392A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51623 AN: 151936 Hom.: 8941 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.340 AC: 51665 AN: 152054 Hom.: 8952 Cov.: 32 AF XY: 0.334 AC XY: 24818 AN XY: 74308

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.329

Alfa AF: 0.325 Hom.: 1406

Bravo AF: 0.339

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.0010
Dann	Benign	0.58

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: rs734640; hg19: chr11-17613348;