Variant chr14-30874833-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000216361.9(COCH):c.-106A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,325,606 control chromosomes in the GnomAD database, including 9,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1006 hom., cov: 33)

Exomes 𝑓: 0.12 ( 8418 hom. )

Consequence

COCH
ENST00000216361.9 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.671

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]

COCH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 14-30874833-A-G is Benign according to our data. Variant chr14-30874833-A-G is described in ClinVar as [Benign]. Clinvar id is 682803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COCH	NM_004086.3 linkuse as main transcript	c.-23-83A>G		intron_variant		ENST00000396618.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COCH	ENST00000396618.9 linkuse as main transcript	c.-23-83A>G		intron_variant		1	NM_004086.3	P1	O43405-1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17025

AN:

151826

Hom.:

1004

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0943

Gnomad AMI

AF:

0.239

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.0919

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0937

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.123

GnomAD4 exome

AF:

0.117

AC:

137616

AN:

1173662

Hom.:

8418

Cov.:

AF XY:

0.118

AC XY:

70460

AN XY:

596596

show subpopulations

Gnomad4 AFR exome

AF:

0.0929

Gnomad4 AMR exome

AF:

0.0727

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.0803

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.122

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.112

AC:

17031

AN:

151944

Hom.:

1006

Cov.:

AF XY:

0.112

AC XY:

8302

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0944

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.147

Gnomad4 EAS

AF:

0.0921

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.0937

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.112

Hom.:

918

Bravo

AF:

0.112

Asia WGS

AF:

0.101

AC:

350

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.0

DANN

Benign

0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over