14-30875307-C-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_004086.3(COCH):c.82+204C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 721,896 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0058 ( 21 hom., cov: 32)
Exomes 𝑓: 0.0031 ( 49 hom. )
Consequence
COCH
NM_004086.3 intron
NM_004086.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.372
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 (BayesDel_noAF=-0.78).
BP6
Variant 14-30875307-C-G is Benign according to our data. Variant chr14-30875307-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1190096.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00575 (876/152346) while in subpopulation AMR AF= 0.0397 (608/15308). AF 95% confidence interval is 0.0371. There are 21 homozygotes in gnomad4. There are 552 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 21 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COCH | NM_004086.3 | c.82+204C>G | intron_variant | ENST00000396618.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COCH | ENST00000396618.9 | c.82+204C>G | intron_variant | 1 | NM_004086.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00577 AC: 879AN: 152228Hom.: 22 Cov.: 32
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GnomAD4 exome AF: 0.00311 AC: 1769AN: 569550Hom.: 49 Cov.: 7 AF XY: 0.00284 AC XY: 843AN XY: 296722
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GnomAD4 genome AF: 0.00575 AC: 876AN: 152346Hom.: 21 Cov.: 32 AF XY: 0.00741 AC XY: 552AN XY: 74496
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 21, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at