10-71439831-C-T

Variant summary

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

The NM_022124.6(CDH23):c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,560,814 control chromosomes in the GnomAD database, including 2,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 1120 hom., cov: 33)

Exomes 𝑓: 0.028 ( 1451 hom. )

Consequence

CDH23
NM_022124.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.36

Variant links:

Genes affected

CDH23 (HGNC:13733): (cadherin related 23) This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described. [provided by RefSeq, May 2013]

CDH23 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=-0.53).

BP6

Variant 10-71439831-C-T is Benign according to our data. Variant chr10-71439831-C-T is described in ClinVar as [Benign]. Clinvar id is 162864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71439831-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH23	NM_022124.6 linkuse as main transcript	c.-1C>T		5_prime_UTR_variant	2/70	ENST00000224721.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.-1C>T		5_prime_UTR_variant	2/70	5	NM_022124.6	P1	Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.0791

AC:

12030

AN:

152086

Hom.:

1109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0408

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0540

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0235

Gnomad OTH

AF:

0.0677

GnomAD3 exomes

AF:

0.0367

AC:

6339

AN:

172822

Hom.:

344

AF XY:

0.0347

AC XY:

3189

AN XY:

91872

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.0232

Gnomad ASJ exome

AF:

0.0355

Gnomad EAS exome

AF:

0.000720

Gnomad SAS exome

AF:

0.0484

Gnomad FIN exome

AF:

0.0202

Gnomad NFE exome

AF:

0.0239

Gnomad OTH exome

AF:

0.0383

GnomAD4 exome

AF:

0.0283

AC:

39816

AN:

1408608

Hom.:

1451

Cov.:

AF XY:

0.0284

AC XY:

19766

AN XY:

695958

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.0259

Gnomad4 ASJ exome

AF:

0.0353

Gnomad4 EAS exome

AF:

0.000189

Gnomad4 SAS exome

AF:

0.0484

Gnomad4 FIN exome

AF:

0.0226

Gnomad4 NFE exome

AF:

0.0213

Gnomad4 OTH exome

AF:

0.0382

GnomAD4 genome

AF:

0.0794

AC:

12084

AN:

152206

Hom.:

1120

Cov.:

AF XY:

0.0771

AC XY:

5736

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.0407

Gnomad4 ASJ

AF:

0.0334

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0536

Gnomad4 FIN

AF:

0.0189

Gnomad4 NFE

AF:

0.0235

Gnomad4 OTH

AF:

0.0670

Alfa

AF:

0.0514

Hom.:

345

Bravo

AF:

0.0858

Asia WGS

AF:

0.0390

AC:

134

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Usher syndrome type 1D

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Autosomal recessive nonsyndromic hearing loss 12

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 30, 2010

-1C>T in the 5'UTR of CDH23: This variant is listed in dbSNP with an allele freq uency of 38% in the Black population (rs41281302) and has previously been report ed as non-pathogenic due to identification in control individuals (Astuto 2002). -

Usher syndrome type 1

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Benign

0.83

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