14-30875200-T-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The ENST00000216361.9(COCH):c.179T>G(p.Leu60Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,496,832 control chromosomes in the GnomAD database, including 747,961 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 1.0 ( 75896 hom., cov: 33)
Exomes 𝑓: 1.0 ( 672065 hom. )
Consequence
COCH
ENST00000216361.9 missense
ENST00000216361.9 missense
Scores
6
Clinical Significance
Conservation
PhyloP100: -1.23
Genes affected
COCH (HGNC:2180): (cochlin) The protein encoded by this gene is highly conserved in human, mouse, and chicken, showing 94% and 79% amino acid identity of human to mouse and chicken sequences, respectively. Hybridization to this gene was detected in spindle-shaped cells located along nerve fibers between the auditory ganglion and sensory epithelium. These cells accompany neurites at the habenula perforata, the opening through which neurites extend to innervate hair cells. This and the pattern of expression of this gene in chicken inner ear paralleled the histologic findings of acidophilic deposits, consistent with mucopolysaccharide ground substance, in temporal bones from DFNA9 (autosomal dominant nonsyndromic sensorineural deafness 9) patients. Mutations that cause DFNA9 have been reported in this gene. Alternative splicing results in multiple transcript variants encoding the same protein. Additional splice variants encoding distinct isoforms have been described but their biological validities have not been demonstrated. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=3.6022067E-4).
BP6
?
Variant 14-30875200-T-G is Benign according to our data. Variant chr14-30875200-T-G is described in ClinVar as [Benign]. Clinvar id is 1182286.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COCH | NM_004086.3 | c.82+97T>G | intron_variant | ENST00000396618.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COCH | ENST00000396618.9 | c.82+97T>G | intron_variant | 1 | NM_004086.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.998 AC: 151921AN: 152170Hom.: 75837 Cov.: 33
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GnomAD4 exome AF: 1.00 AC: 1344335AN: 1344544Hom.: 672065 Cov.: 23 AF XY: 1.00 AC XY: 662849AN XY: 662946
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GnomAD4 genome ? AF: 0.998 AC: 152039AN: 152288Hom.: 75896 Cov.: 33 AF XY: 0.998 AC XY: 74328AN XY: 74448
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3708
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3854
Asia WGS
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3476
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 22, 2018 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MutationTaster
Benign
P;P;P;P
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at