rs3802720

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022124.6(CDH23):c.366T>C(p.Val122Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,613,518 control chromosomes in the GnomAD database, including 367,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 42372 hom., cov: 32)

Exomes 𝑓: 0.66 ( 325004 hom. )

Consequence

CDH23
NM_022124.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -1.73

Publications

30 publications found

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:

CDH23-AS1 (HGNC:31433): (CDH23 antisense RNA 1)

CDH23-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-71511149-T-C is Benign according to our data. Variant chr10-71511149-T-C is described in ClinVar as Benign. ClinVar VariationId is 45928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.366T>C	p.Val122Val	synonymous_variant	Exon 6 of 70	ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 link	c.366T>C	p.Val122Val	synonymous_variant	Exon 6 of 70	5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.734

AC:

111543

AN:

151966

Hom.:

42323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.930

Gnomad AMI

AF:

0.495

Gnomad AMR

AF:

0.579

Gnomad ASJ

AF:

0.735

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.700

GnomAD2 exomes

AF:

0.661

AC:

164866

AN:

249270

AF XY:

0.660

show subpopulations

Gnomad AFR exome

AF:

0.940

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.733

Gnomad EAS exome

AF:

0.778

Gnomad FIN exome

AF:

0.733

Gnomad NFE exome

AF:

0.663

Gnomad OTH exome

AF:

0.660

GnomAD4 exome

AF:

0.664

AC:

969722

AN:

1461434

Hom.:

325004

Cov.:

AF XY:

0.662

AC XY:

481285

AN XY:

727026

show subpopulations

African (AFR)

AF:

0.944

AC:

31596

AN:

33480

American (AMR)

AF:

0.469

AC:

20957

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.728

AC:

19015

AN:

26136

East Asian (EAS)

AF:

0.758

AC:

30110

AN:

39698

South Asian (SAS)

AF:

0.607

AC:

52324

AN:

86252

European-Finnish (FIN)

AF:

0.726

AC:

38752

AN:

53382

Middle Eastern (MID)

AF:

0.700

AC:

4037

AN:

5768

European-Non Finnish (NFE)

AF:

0.658

AC:

731668

AN:

1111624

Other (OTH)

AF:

0.683

AC:

41263

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

18156

36312

54468

72624

90780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19112

38224

57336

76448

95560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.734

AC:

111644

AN:

152084

Hom.:

42372

Cov.:

AF XY:

0.734

AC XY:

54512

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.930

AC:

38609

AN:

41516

American (AMR)

AF:

0.578

AC:

8838

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.735

AC:

2551

AN:

3472

East Asian (EAS)

AF:

0.777

AC:

4010

AN:

5158

South Asian (SAS)

AF:

0.597

AC:

2875

AN:

4818

European-Finnish (FIN)

AF:

0.747

AC:

7896

AN:

10568

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.659

AC:

44759

AN:

67956

Other (OTH)

AF:

0.697

AC:

1467

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1459

2919

4378

5838

7297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.679

Hom.:

54818

Bravo

AF:

0.727

Asia WGS

AF:

0.684

AC:

2379

AN:

3478

EpiCase

AF:

0.655

EpiControl

AF:

0.654

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 02, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Inferred frequency = 136/301 -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 1D

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 12

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 1

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.18

(source)

DANN

Benign

0.65

PhyloP100

-1.7

PromoterAI

0.017

Neutral

(source)

Mutation Taster

=83/17

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over