chr14-30877576-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_004086.3(COCH):c.87C>T(p.Pro29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
COCH
NM_004086.3 synonymous
NM_004086.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.122
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 -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 14-30877576-C-T is Benign according to our data. Variant chr14-30877576-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 595709.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.122 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000164 (25/152216) while in subpopulation AMR AF= 0.00164 (25/15278). AF 95% confidence interval is 0.00114. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COCH | NM_004086.3 | c.87C>T | p.Pro29= | synonymous_variant | 4/12 | ENST00000396618.9 | |
LOC100506071 | NR_038356.1 | n.1618-1024G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COCH | ENST00000396618.9 | c.87C>T | p.Pro29= | synonymous_variant | 4/12 | 1 | NM_004086.3 | P1 | |
ENST00000555108.1 | n.1618-1024G>A | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251430Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135906
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461838Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727222
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 15, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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