Variant rs7068810 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 NM_022124.6(CDH23):c.5503-44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,528,944 control chromosomes in the GnomAD database, including 28,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3220 hom., cov: 33)

Exomes 𝑓: 0.19 ( 25214 hom. )

Consequence

CDH23
NM_022124.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.66

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 10-71784847-T-C is Benign according to our data. Variant chr10-71784847-T-C is described in ClinVar as [Benign]. Clinvar id is 261552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71784847-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 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.5503-44T>C		intron_variant		ENST00000224721.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.5503-44T>C		intron_variant		5	NM_022124.6	P1	Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30718

AN:

152042

Hom.:

3217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.218

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.196

GnomAD3 exomes

AF:

0.181

AC:

44377

AN:

245768

Hom.:

4205

AF XY:

0.177

AC XY:

23541

AN XY:

133314

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.238

Gnomad SAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.213

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.188

AC:

259323

AN:

1376784

Hom.:

25214

Cov.:

AF XY:

0.186

AC XY:

127884

AN XY:

689394

show subpopulations

Gnomad4 AFR exome

AF:

0.259

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.161

Gnomad4 EAS exome

AF:

0.272

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.190

Gnomad4 OTH exome

AF:

0.186

GnomAD4 genome

AF:

0.202

AC:

30738

AN:

152160

Hom.:

3220

Cov.:

AF XY:

0.201

AC XY:

14961

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.249

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.218

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.194

Alfa

AF:

0.184

Hom.:

4726

Bravo

AF:

0.201

Asia WGS

AF:

0.151

AC:

526

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Usher syndrome type 1D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 13, 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. -

Autosomal recessive nonsyndromic hearing loss 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

DANN

Benign

0.38

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

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