rs1867998

chr10-71575285-T-C

Variant summary

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

The NM_022124.6(CDH23):c.754-2629T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,032 control chromosomes in the GnomAD database, including 35,159 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 0.66 (35159 hom., cov: 32)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.93

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH23	NM_022124.6	c.754-2629T>C		intron_variant		ENST00000224721.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12	c.754-2629T>C		intron_variant		5	NM_022124.6	P1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100349 AN: 151914 Hom.: 35113 Cov.: 32

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.661 AC: 100451 AN: 152032 Hom.: 35159 Cov.: 32 AF XY: 0.661 AC XY: 49088 AN XY: 74294

Gnomad4 AFR AF: 0.893

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.630

Alfa AF: 0.568 Hom.: 11440

Bravo AF: 0.673

Asia WGS AF: 0.751 AC: 2612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
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

Other links and lift over

dbSNP: rs1867998; hg19: chr10-73335042;