chr14-30875191-C-T

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

Scores

6

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.215
Variant links:
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]

Genome browser will be placed here

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
COCHNM_004086.3 linkuse as main transcriptc.82+88C>T intron_variant ENST00000396618.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COCHENST00000396618.9 linkuse as main transcriptc.82+88C>T intron_variant 1 NM_004086.3 P1O43405-1

Frequencies

GnomAD3 genomes
AF:
0.00103
AC:
156
AN:
152170
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0290
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000671
AC:
916
AN:
1366112
Hom.:
8
Cov.:
26
AF XY:
0.000730
AC XY:
492
AN XY:
673736
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000285
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0221
Gnomad4 SAS exome
AF:
0.000833
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000113
Gnomad4 OTH exome
AF:
0.000914
GnomAD4 genome
AF:
0.00102
AC:
156
AN:
152288
Hom.:
1
Cov.:
33
AF XY:
0.00118
AC XY:
88
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0291
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000371
Hom.:
0
Bravo
AF:
0.00133
Asia WGS
AF:
0.00895
AC:
31
AN:
3478

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 submitterclinical testingPreventionGenetics, part of Exact SciencesApr 05, 2019This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
7.1
DANN
Benign
0.77
FATHMM_MKL
Benign
0.052
N
LIST_S2
Benign
0.26
T
MetaRNN
Benign
0.0039
T
MutationTaster
Benign
1.0
N;N;N;N
GERP RS
-0.34
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.27
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.27
Position offset: 6

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: rs56946687; hg19: chr14-31344397; API