rs3802719

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022124.6(CDH23):c.429+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,610,480 control chromosomes in the GnomAD database, including 364,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 41212 hom., cov: 33)

Exomes 𝑓: 0.66 ( 323219 hom. )

Consequence

CDH23
NM_022124.6 intron

Scores

Splicing: ADA: 0.00001863

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.66

Publications

11 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.008).

BP6

Variant 10-71511225-G-A is Benign according to our data. Variant chr10-71511225-G-A is described in ClinVar as Benign. ClinVar VariationId is 45940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.429+13G>A		intron_variant	Intron 6 of 69	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.429+13G>A		intron_variant	Intron 6 of 69	5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.726

AC:

110146

AN:

151694

Hom.:

41167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.905

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.734

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.746

Gnomad MID

AF:

0.634

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.696

GnomAD2 exomes

AF:

0.659

AC:

164153

AN:

249118

AF XY:

0.658

show subpopulations

Gnomad AFR exome

AF:

0.917

Gnomad AMR exome

AF:

0.456

Gnomad ASJ exome

AF:

0.733

Gnomad EAS exome

AF:

0.780

Gnomad FIN exome

AF:

0.733

Gnomad NFE exome

AF:

0.663

Gnomad OTH exome

AF:

0.658

GnomAD4 exome

AF:

0.662

AC:

966220

AN:

1458666

Hom.:

323219

Cov.:

AF XY:

0.661

AC XY:

479683

AN XY:

725832

show subpopulations

African (AFR)

AF:

0.921

AC:

30773

AN:

33428

American (AMR)

AF:

0.466

AC:

20857

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.728

AC:

19004

AN:

26118

East Asian (EAS)

AF:

0.758

AC:

30097

AN:

39694

South Asian (SAS)

AF:

0.603

AC:

51942

AN:

86182

European-Finnish (FIN)

AF:

0.726

AC:

38723

AN:

53352

Middle Eastern (MID)

AF:

0.698

AC:

4022

AN:

5760

European-Non Finnish (NFE)

AF:

0.658

AC:

729767

AN:

1109146

Other (OTH)

AF:

0.681

AC:

41035

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

15024

30047

45071

60094

75118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19040

38080

57120

76160

95200

<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:

0.726

AC:

110241

AN:

151814

Hom.:

41212

Cov.:

AF XY:

0.726

AC XY:

53842

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.905

AC:

37524

AN:

41470

American (AMR)

AF:

0.575

AC:

8782

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.734

AC:

2544

AN:

3464

East Asian (EAS)

AF:

0.778

AC:

4007

AN:

5152

South Asian (SAS)

AF:

0.591

AC:

2843

AN:

4814

European-Finnish (FIN)

AF:

0.746

AC:

7846

AN:

10516

Middle Eastern (MID)

AF:

0.637

AC:

186

AN:

292

European-Non Finnish (NFE)

AF:

0.658

AC:

44603

AN:

67824

Other (OTH)

AF:

0.693

AC:

1460

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1469

2938

4406

5875

7344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.680

Hom.:

140595

Bravo

AF:

0.719

Asia WGS

AF:

0.676

AC:

2354

AN:

3478

EpiCase

AF:

0.654

EpiControl

AF:

0.653

ClinVar

Significance: Benign

Submissions summary: Benign:11

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

- -

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 = 185/301 -

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

- -

not provided

Benign:3

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

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 1D

Benign:2

Jan 13, 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

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.013

(source)

DANN

Benign

0.72

PhyloP100

-2.7

PromoterAI

-0.017

Neutral

(source)

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0

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

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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