rs17097458

Variant names:

• chr14-30886321-C-A
• rs17097458
• NM_004086.3:c.1477+9C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-30886321-C-A
• chr14-30886321-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004086.3(COCH):​c.1477+9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 1,613,692 control chromosomes in the GnomAD database, including 3,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (302 hom., cov: 33)
  • Exomes 𝑓: 0.059 (3167 hom.)
• Consequence: COCH NM_004086.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.328

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]

ENSG00000258525 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 14-30886321-C-A is Benign according to our data. Variant chr14-30886321-C-A is described in ClinVar as [Benign]. Clinvar id is 226528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-30886321-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COCH	NM_004086.3	c.1477+9C>A		intron_variant	Intron 11 of 11	ENST00000396618.9	NP_004077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COCH	ENST00000396618.9	c.1477+9C>A		intron_variant	Intron 11 of 11	1	NM_004086.3	ENSP00000379862.3

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8112 AN: 152128 Hom.: 301 Cov.: 33

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.0276

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.0840

Gnomad FIN AF: 0.0710

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.0516

GnomAD3 exomes AF: 0.0667 AC: 16628 AN: 249448 Hom.: 753 AF XY: 0.0675 AC XY: 9134 AN XY: 135312

Gnomad AFR exome AF: 0.0247

Gnomad AMR exome AF: 0.0655

Gnomad ASJ exome AF: 0.0300

Gnomad EAS exome AF: 0.176

Gnomad SAS exome AF: 0.0898

Gnomad FIN exome AF: 0.0647

Gnomad NFE exome AF: 0.0529

Gnomad OTH exome AF: 0.0563

GnomAD4 exome AF: 0.0592 AC: 86463 AN: 1461446 Hom.: 3167 Cov.: 34 AF XY: 0.0601 AC XY: 43695 AN XY: 727048

Gnomad4 AFR exome AF: 0.0223

Gnomad4 AMR exome AF: 0.0666

Gnomad4 ASJ exome AF: 0.0291

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.0907

Gnomad4 FIN exome AF: 0.0655

Gnomad4 NFE exome AF: 0.0539

Gnomad4 OTH exome AF: 0.0603

GnomAD4 genome AF: 0.0533 AC: 8122 AN: 152246 Hom.: 302 Cov.: 33 AF XY: 0.0557 AC XY: 4147 AN XY: 74428

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.0276

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.0840

Gnomad4 FIN AF: 0.0710

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0517 Hom.: 182

Bravo AF: 0.0510

Asia WGS AF: 0.138 AC: 479 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

1477+9C>A in Intron 11 of COCH: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce and has been identified in 5.3% (369/7014) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs17097458). -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 03, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 9 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.6
DANN	Benign	0.64
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

Other links and lift over

dbSNP: rs17097458; hg19: chr14-31355527;