11-17635139-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001292063.2(OTOG):​c.7645C>T​(p.Leu2549=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,548,856 control chromosomes in the GnomAD database, including 13,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1165 hom., cov: 32)
Exomes 𝑓: 0.13 ( 12634 hom. )

Consequence

OTOG
NM_001292063.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.29
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 11-17635139-C-T is Benign according to our data. Variant chr11-17635139-C-T is described in ClinVar as [Benign]. Clinvar id is 226911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17635139-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=1.29 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OTOGNM_001292063.2 linkuse as main transcriptc.7645C>T p.Leu2549= synonymous_variant 46/56 ENST00000399397.6 NP_001278992.1
OTOGNM_001277269.2 linkuse as main transcriptc.7681C>T p.Leu2561= synonymous_variant 45/55 NP_001264198.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OTOGENST00000399397.6 linkuse as main transcriptc.7645C>T p.Leu2549= synonymous_variant 46/565 NM_001292063.2 ENSP00000382329 P2
OTOGENST00000399391.7 linkuse as main transcriptc.7681C>T p.Leu2561= synonymous_variant 45/555 ENSP00000382323 A2Q6ZRI0-1
OTOGENST00000342528.2 linkuse as main transcriptn.4606-471C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.118
AC:
17885
AN:
151960
Hom.:
1166
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0771
Gnomad AMI
AF:
0.254
Gnomad AMR
AF:
0.0931
Gnomad ASJ
AF:
0.152
Gnomad EAS
AF:
0.233
Gnomad SAS
AF:
0.183
Gnomad FIN
AF:
0.120
Gnomad MID
AF:
0.136
Gnomad NFE
AF:
0.130
Gnomad OTH
AF:
0.128
GnomAD3 exomes
AF:
0.133
AC:
18923
AN:
141776
Hom.:
1485
AF XY:
0.139
AC XY:
10687
AN XY:
76814
show subpopulations
Gnomad AFR exome
AF:
0.0756
Gnomad AMR exome
AF:
0.0685
Gnomad ASJ exome
AF:
0.151
Gnomad EAS exome
AF:
0.250
Gnomad SAS exome
AF:
0.175
Gnomad FIN exome
AF:
0.122
Gnomad NFE exome
AF:
0.130
Gnomad OTH exome
AF:
0.135
GnomAD4 exome
AF:
0.131
AC:
183533
AN:
1396778
Hom.:
12634
Cov.:
34
AF XY:
0.134
AC XY:
91989
AN XY:
688866
show subpopulations
Gnomad4 AFR exome
AF:
0.0809
Gnomad4 AMR exome
AF:
0.0709
Gnomad4 ASJ exome
AF:
0.151
Gnomad4 EAS exome
AF:
0.213
Gnomad4 SAS exome
AF:
0.174
Gnomad4 FIN exome
AF:
0.118
Gnomad4 NFE exome
AF:
0.129
Gnomad4 OTH exome
AF:
0.141
GnomAD4 genome
AF:
0.118
AC:
17883
AN:
152078
Hom.:
1165
Cov.:
32
AF XY:
0.119
AC XY:
8827
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.0770
Gnomad4 AMR
AF:
0.0929
Gnomad4 ASJ
AF:
0.152
Gnomad4 EAS
AF:
0.233
Gnomad4 SAS
AF:
0.183
Gnomad4 FIN
AF:
0.120
Gnomad4 NFE
AF:
0.130
Gnomad4 OTH
AF:
0.126
Alfa
AF:
0.127
Hom.:
1475
Bravo
AF:
0.112
Asia WGS
AF:
0.202
AC:
704
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
Benign, criteria provided, single submitterclinical testingGeneDxMay 09, 2017This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineNov 24, 2014Leu2561Leu in exon 45 of OTOG: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 18.5% (37/200) of H an Chinese chromosomes from a broad population by the 1000 Genomes Project (http ://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs11024350). -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
5.1
DANN
Benign
0.66

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

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

Other links and lift over

dbSNP: rs11024350; hg19: chr11-17656686; API