Variant rs538124093 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001292063.2(OTOG):c.7585+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000651 in 1,517,650 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 4 hom. )

Consequence

OTOG
NM_001292063.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.09

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-17634960-G-A is Benign according to our data. Variant chr11-17634960-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTOG	NM_001292063.2 linkuse as main transcript	c.7585+12G>A		intron_variant		ENST00000399397.6
OTOG	NM_001277269.2 linkuse as main transcript	c.7621+12G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
OTOG	ENST00000399397.6 linkuse as main transcript	c.7585+12G>A	intron_variant	5	NM_001292063.2	P2
OTOG	ENST00000399391.7 linkuse as main transcript	c.7621+12G>A	intron_variant	5		A2	Q6ZRI0-1
OTOG	ENST00000342528.2 linkuse as main transcript	n.4606-650G>A	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00307

AC:

466

AN:

151728

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00434

GnomAD3 exomes

AF:

0.000720

AC:

102

AN:

141610

Hom.:

AF XY:

0.000546

AC XY:

AN XY:

76884

show subpopulations

Gnomad AFR exome

AF:

0.0120

Gnomad AMR exome

AF:

0.000835

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000117

Gnomad OTH exome

AF:

0.000243

GnomAD4 exome

AF:

0.000373

AC:

510

AN:

1365804

Hom.:

Cov.:

AF XY:

0.000332

AC XY:

224

AN XY:

674910

show subpopulations

Gnomad4 AFR exome

AF:

0.0105

Gnomad4 AMR exome

AF:

0.000845

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000932

Gnomad4 OTH exome

AF:

0.00100

GnomAD4 genome

AF:

0.00315

AC:

478

AN:

151846

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

231

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.0109

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00429

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.00345

Asia WGS

AF:

0.00115

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jan 15, 2016

c.7621+12G>A in intron 44 of OTOG: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence and it has been identified in 1.25% (5/398) of African chromosomes by the Exome Agg regation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs538124093). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

Cadd

Benign

0.0010

Dann

Benign

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over