chr14-30875191-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The ENST00000216361.9(COCH):c.170C>T(p.Ala57Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000706 in 1,518,400 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.0010 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00067 ( 8 hom. )
Consequence
COCH
ENST00000216361.9 missense
ENST00000216361.9 missense
Scores
6
Clinical Significance
Conservation
PhyloP100: 0.215
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 -9 ACMG points.
BP6
Variant 14-30875191-C-T is Benign according to our data. Variant chr14-30875191-C-T is described in ClinVar as [Benign]. Clinvar id is 3055531.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00102 (156/152288) while in subpopulation EAS AF= 0.0291 (150/5156). AF 95% confidence interval is 0.0253. There are 1 homozygotes in gnomad4. There are 88 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COCH | NM_004086.3 | c.82+88C>T | intron_variant | ENST00000396618.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COCH | ENST00000396618.9 | c.82+88C>T | intron_variant | 1 | NM_004086.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00103 AC: 156AN: 152170Hom.: 1 Cov.: 33
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GnomAD4 exome AF: 0.000671 AC: 916AN: 1366112Hom.: 8 Cov.: 26 AF XY: 0.000730 AC XY: 492AN XY: 673736
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GnomAD4 genome AF: 0.00102 AC: 156AN: 152288Hom.: 1 Cov.: 33 AF XY: 0.00118 AC XY: 88AN XY: 74452
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
COCH-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 05, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MutationTaster
Benign
N;N;N;N
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 6
Find out detailed SpliceAI scores and Pangolin per-transcript scores at