Variant chr10-71509957-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.146-125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,049,302 control chromosomes in the GnomAD database, including 242,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 42171 hom., cov: 31)

Exomes 𝑓: 0.66 ( 200565 hom. )

Consequence

CDH23
NM_022124.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.12

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:

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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=-0.93).

BP6

Variant 10-71509957-T-C is Benign according to our data. Variant chr10-71509957-T-C is described in ClinVar as [Benign]. Clinvar id is 678765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.146-125T>C		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 link	c.146-125T>C		intron_variant		5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.732

AC:

111327

AN:

151984

Hom.:

42123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.925

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.579

Gnomad ASJ

AF:

0.735

Gnomad EAS

AF:

0.776

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.748

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.697

GnomAD4 exome

AF:

0.665

AC:

596197

AN:

897200

Hom.:

200565

Cov.:

AF XY:

0.662

AC XY:

304995

AN XY:

460724

show subpopulations

Gnomad4 AFR exome

AF:

0.935

Gnomad4 AMR exome

AF:

0.472

Gnomad4 ASJ exome

AF:

0.728

Gnomad4 EAS exome

AF:

0.756

Gnomad4 SAS exome

AF:

0.606

Gnomad4 FIN exome

AF:

0.723

Gnomad4 NFE exome

AF:

0.660

Gnomad4 OTH exome

AF:

0.686

GnomAD4 genome

AF:

0.733

AC:

111427

AN:

152102

Hom.:

42171

Cov.:

AF XY:

0.732

AC XY:

54417

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.925

Gnomad4 AMR

AF:

0.578

Gnomad4 ASJ

AF:

0.735

Gnomad4 EAS

AF:

0.777

Gnomad4 SAS

AF:

0.597

Gnomad4 FIN

AF:

0.748

Gnomad4 NFE

AF:

0.658

Gnomad4 OTH

AF:

0.694

Alfa

AF:

0.708

Hom.:

4826

Bravo

AF:

0.726

Asia WGS

AF:

0.682

AC:

2372

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 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. -

Pituitary adenoma 5, multiple types

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Usher syndrome type 1D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Autosomal recessive nonsyndromic hearing loss 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.013

DANN

Benign

0.32

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