Variant chr10-71777631-T-C 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.4846-49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,525,420 control chromosomes in the GnomAD database, including 156,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13259 hom., cov: 31)

Exomes 𝑓: 0.46 ( 143492 hom. )

Consequence

CDH23
NM_022124.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.720

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=-0.89).

BP6

Variant 10-71777631-T-C is Benign according to our data. Variant chr10-71777631-T-C is described in ClinVar as [Benign]. Clinvar id is 261550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71777631-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6 linkuse as main transcript	c.4846-49T>C		intron_variant		ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.4846-49T>C		intron_variant		5	NM_022124.6	ENSP00000224721	P1	Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

62966

AN:

151864

Hom.:

13246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.417

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.410

GnomAD3 exomes

AF:

0.442

AC:

77644

AN:

175702

Hom.:

17419

AF XY:

0.436

AC XY:

40883

AN XY:

93872

show subpopulations

Gnomad AFR exome

AF:

0.328

Gnomad AMR exome

AF:

0.480

Gnomad ASJ exome

AF:

0.417

Gnomad EAS exome

AF:

0.490

Gnomad SAS exome

AF:

0.380

Gnomad FIN exome

AF:

0.460

Gnomad NFE exome

AF:

0.455

Gnomad OTH exome

AF:

0.432

GnomAD4 exome

AF:

0.455

AC:

625185

AN:

1373438

Hom.:

143492

Cov.:

AF XY:

0.452

AC XY:

307274

AN XY:

679684

show subpopulations

Gnomad4 AFR exome

AF:

0.327

Gnomad4 AMR exome

AF:

0.476

Gnomad4 ASJ exome

AF:

0.420

Gnomad4 EAS exome

AF:

0.522

Gnomad4 SAS exome

AF:

0.382

Gnomad4 FIN exome

AF:

0.453

Gnomad4 NFE exome

AF:

0.464

Gnomad4 OTH exome

AF:

0.443

GnomAD4 genome

AF:

0.415

AC:

63012

AN:

151982

Hom.:

13259

Cov.:

AF XY:

0.413

AC XY:

30673

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.336

Gnomad4 AMR

AF:

0.418

Gnomad4 ASJ

AF:

0.417

Gnomad4 EAS

AF:

0.481

Gnomad4 SAS

AF:

0.379

Gnomad4 FIN

AF:

0.454

Gnomad4 NFE

AF:

0.453

Gnomad4 OTH

AF:

0.408

Alfa

AF:

0.442

Hom.:

26351

Bravo

AF:

0.411

Asia WGS

AF:

0.406

AC:

1412

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	- -

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

- -

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

-0.89

CADD

Benign

4.0

DANN

Benign

0.52

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