chr14-30877304-C-A

Variant names:

• chr14-30877304-C-A
• rs2284654
• NM_004086.3:c.83-268C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004086.3(COCH):​c.83-268C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 407,546 control chromosomes in the GnomAD database, including 865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (609 hom., cov: 32)
  • Exomes 𝑓: 0.030 (256 hom.)
• Consequence: COCH NM_004086.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.500

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 14-30877304-C-A is Benign according to our data. Variant chr14-30877304-C-A is described in ClinVar as [Benign]. Clinvar id is 1241517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COCH	NM_004086.3	c.83-268C>A		intron_variant	Intron 3 of 11	ENST00000396618.9	NP_004077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COCH	ENST00000396618.9	c.83-268C>A		intron_variant	Intron 3 of 11	1	NM_004086.3	ENSP00000379862.3

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9455 AN: 151332 Hom.: 610 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0988

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0437

GnomAD4 exome AF: 0.0296 AC: 7591 AN: 256096 Hom.: 256 Cov.: 3 AF XY: 0.0293 AC XY: 4027 AN XY: 137444

Gnomad4 AFR exome AF: 0.162 AC: 1216 AN: 7508

Gnomad4 AMR exome AF: 0.0180 AC: 207 AN: 11530

Gnomad4 ASJ exome AF: 0.00410 AC: 29 AN: 7072

Gnomad4 EAS exome AF: 0.101 AC: 1348 AN: 13364

Gnomad4 SAS exome AF: 0.0260 AC: 1012 AN: 38932

Gnomad4 FIN exome AF: 0.0110 AC: 126 AN: 11454

Gnomad4 NFE exome AF: 0.0213 AC: 3224 AN: 151494

Gnomad4 Remaining exome AF: 0.0302 AC: 414 AN: 13724

GnomAD4 genome AF: 0.0625 AC: 9465 AN: 151450 Hom.: 609 Cov.: 32 AF XY: 0.0618 AC XY: 4577 AN XY: 74038

Gnomad4 AFR AF: 0.162 AC: 0.162007 AN: 0.162007

Gnomad4 AMR AF: 0.0281 AC: 0.0281311 AN: 0.0281311

Gnomad4 ASJ AF: 0.00202 AC: 0.00202079 AN: 0.00202079

Gnomad4 EAS AF: 0.0986 AC: 0.0986052 AN: 0.0986052

Gnomad4 SAS AF: 0.0310 AC: 0.0309643 AN: 0.0309643

Gnomad4 FIN AF: 0.0174 AC: 0.0174375 AN: 0.0174375

Gnomad4 NFE AF: 0.0209 AC: 0.020902 AN: 0.020902

Gnomad4 OTH AF: 0.0446 AC: 0.0446344 AN: 0.0446344

Alfa AF: 0.0309 Hom.: 251

Bravo AF: 0.0673

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.7
DANN	Benign	0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs2284654; hg19: chr14-31346510;