10-71439744-C-A

Position:

• chr10-71439744-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022124.6(CDH23):​c.-5-83C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 960,604 control chromosomes in the GnomAD database, including 101,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (12204 hom., cov: 33)
  • Exomes 𝑓: 0.46 (89143 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.127

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 10-71439744-C-A is Benign according to our data. Variant chr10-71439744-C-A is described in ClinVar as [Benign]. Clinvar id is 670320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6	c.-5-83C>A		intron_variant		ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.-5-83C>A		intron_variant		5	NM_022124.6	ENSP00000224721	P1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54646 AN: 152050 Hom.: 12205 Cov.: 33

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.461 AC: 372774 AN: 808436 Hom.: 89143 AF XY: 0.458 AC XY: 189945 AN XY: 414362

Gnomad4 AFR exome AF: 0.0858

Gnomad4 AMR exome AF: 0.381

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.551

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.503

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.359 AC: 54641 AN: 152168 Hom.: 12204 Cov.: 33 AF XY: 0.362 AC XY: 26902 AN XY: 74392

Gnomad4 AFR AF: 0.0894

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.354

Alfa AF: 0.325 Hom.: 1389

Bravo AF: 0.339

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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. -

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	-0.65
CADD	Benign	4.1
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs4747153; hg19: chr10-73199501;