rs11594082

Positions:

• chr10-71539496-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022124.6(CDH23):​c.430-27246G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 151,638 control chromosomes in the GnomAD database, including 895 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (895 hom., cov: 31)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH23	NM_022124.6	c.430-27246G>T		intron_variant		ENST00000224721.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12	c.430-27246G>T		intron_variant		5	NM_022124.6	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15580 AN: 151520 Hom.: 890 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0815

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000778

Gnomad SAS AF: 0.0368

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.103 AC: 15610 AN: 151638 Hom.: 895 Cov.: 31 AF XY: 0.0996 AC XY: 7381 AN XY: 74078

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0813

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.000780

Gnomad4 SAS AF: 0.0373

Gnomad4 FIN AF: 0.0757

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.106

Alfa AF: 0.108 Hom.: 215

Bravo AF: 0.104

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	14
DANN	Benign	0.76

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: rs11594082; hg19: chr10-73299253;