Variant 14-30875200-T-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.179T>G(p.Leu60Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,496,832 control chromosomes in the GnomAD database, including 747,961 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75896 hom., cov: 33)

Exomes 𝑓: 1.0 ( 672065 hom. )

Consequence

COCH
ENST00000216361.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.23

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 (MetaRNN=3.6022067E-4).

BP6

Variant 14-30875200-T-G is Benign according to our data. Variant chr14-30875200-T-G is described in ClinVar as [Benign]. Clinvar id is 1182286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COCH	NM_004086.3 linkuse as main transcript	c.82+97T>G		intron_variant		ENST00000396618.9	NP_004077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COCH	ENST00000396618.9 linkuse as main transcript	c.82+97T>G		intron_variant		1	NM_004086.3	ENSP00000379862	P1	O43405-1

Frequencies

GnomAD3 genomes

AF:

0.998

AC:

151921

AN:

152170

Hom.:

75837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.994

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.999

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1344335

AN:

1344544

Hom.:

672065

Cov.:

AF XY:

1.00

AC XY:

662849

AN XY:

662946

show subpopulations

Gnomad4 AFR exome

AF:

0.995

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.998

AC:

152039

AN:

152288

Hom.:

75896

Cov.:

AF XY:

0.998

AC XY:

74328

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.994

Gnomad4 AMR

AF:

0.999

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

1.00

Alfa

AF:

1.00

Hom.:

4067

Bravo

AF:

0.998

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3854

Asia WGS

AF:

0.999

AC:

3476

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 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.7

DANN

Benign

0.50

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.18

MetaRNN

Benign

0.00036

MutationTaster

Benign

1.0

P;P;P;P

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.061

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