14-30875307-C-G

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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.372
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 -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
COCHNM_004086.3 linkuse as main transcriptc.82+204C>G intron_variant ENST00000396618.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COCHENST00000396618.9 linkuse as main transcriptc.82+204C>G intron_variant 1 NM_004086.3 P1O43405-1

Frequencies

GnomAD3 genomes
AF:
0.00577
AC:
879
AN:
152228
Hom.:
22
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000579
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0399
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00115
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0158
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000941
Gnomad OTH
AF:
0.00287
GnomAD4 exome
AF:
0.00311
AC:
1769
AN:
569550
Hom.:
49
Cov.:
7
AF XY:
0.00284
AC XY:
843
AN XY:
296722
show subpopulations
Gnomad4 AFR exome
AF:
0.000275
Gnomad4 AMR exome
AF:
0.0500
Gnomad4 ASJ exome
AF:
0.000137
Gnomad4 EAS exome
AF:
0.0000626
Gnomad4 SAS exome
AF:
0.000101
Gnomad4 FIN exome
AF:
0.0118
Gnomad4 NFE exome
AF:
0.000689
Gnomad4 OTH exome
AF:
0.00509
GnomAD4 genome
AF:
0.00575
AC:
876
AN:
152346
Hom.:
21
Cov.:
32
AF XY:
0.00741
AC XY:
552
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.000577
Gnomad4 AMR
AF:
0.0397
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000965
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0158
Gnomad4 NFE
AF:
0.000941
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00234
Hom.:
0
Bravo
AF:
0.00658
Asia WGS
AF:
0.00693
AC:
24
AN:
3478

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 submitterclinical testingGeneDxDec 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.86
DANN
Benign
0.41
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs7158281; hg19: chr14-31344513; API