chr10-71739153-C-T

Position:

• chr10-71739153-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022124.6(CDH23):​c.4360-491C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,068 control chromosomes in the GnomAD database, including 18,783 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 0.47 (18783 hom., cov: 32)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6	c.4360-491C>T		intron_variant		ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.4360-491C>T		intron_variant		5	NM_022124.6	ENSP00000224721	P1
CDH23	ENST00000398792.3	n.1049-491C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72103 AN: 151950 Hom.: 18786 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.474 AC: 72102 AN: 152068 Hom.: 18783 Cov.: 32 AF XY: 0.477 AC XY: 35463 AN XY: 74324

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.524

Alfa AF: 0.570 Hom.: 33187

Bravo AF: 0.455

Asia WGS AF: 0.423 AC: 1471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.82

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: rs10823837; hg19: chr10-73498910;