Variant 10-71739804-C-G 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.4488+32C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,582,254 control chromosomes in the GnomAD database, including 244,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20464 hom., cov: 33)

Exomes 𝑓: 0.56 ( 224380 hom. )

Consequence

CDH23
NM_022124.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.610

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 (HGNC:):

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=-0.91).

BP6

Variant 10-71739804-C-G is Benign according to our data. Variant chr10-71739804-C-G is described in ClinVar as [Benign]. Clinvar id is 261549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71739804-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.586 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.4488+32C>G		intron_variant		ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.4488+32C>G		intron_variant		5	NM_022124.6	ENSP00000224721.9		Q9H251-1
CDH23	ENST00000398792.3 linkuse as main transcript	n.1177+32C>G		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.511

AC:

77684

AN:

151968

Hom.:

20466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.458

Gnomad FIN

AF:

0.562

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.591

Gnomad OTH

AF:

0.537

GnomAD3 exomes

AF:

0.501

AC:

116078

AN:

231556

Hom.:

30281

AF XY:

0.509

AC XY:

64300

AN XY:

126316

show subpopulations

Gnomad AFR exome

AF:

0.407

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.594

Gnomad EAS exome

AF:

0.305

Gnomad SAS exome

AF:

0.454

Gnomad FIN exome

AF:

0.565

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.530

GnomAD4 exome

AF:

0.555

AC:

793870

AN:

1430168

Hom.:

224380

Cov.:

AF XY:

0.554

AC XY:

392103

AN XY:

708262

show subpopulations

Gnomad4 AFR exome

AF:

0.405

Gnomad4 AMR exome

AF:

0.361

Gnomad4 ASJ exome

AF:

0.597

Gnomad4 EAS exome

AF:

0.271

Gnomad4 SAS exome

AF:

0.455

Gnomad4 FIN exome

AF:

0.564

Gnomad4 NFE exome

AF:

0.585

Gnomad4 OTH exome

AF:

0.539

GnomAD4 genome

AF:

0.511

AC:

77693

AN:

152086

Hom.:

20464

Cov.:

AF XY:

0.508

AC XY:

37738

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.414

Gnomad4 AMR

AF:

0.451

Gnomad4 ASJ

AF:

0.595

Gnomad4 EAS

AF:

0.287

Gnomad4 SAS

AF:

0.460

Gnomad4 FIN

AF:

0.562

Gnomad4 NFE

AF:

0.591

Gnomad4 OTH

AF:

0.533

Alfa

AF:

0.510

Hom.:

2858

Bravo

AF:

0.498

Asia WGS

AF:

0.344

AC:

1198

AN:

3478

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	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.91

CADD

Benign

0.50

DANN

Benign

0.47

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