rs1234888

Positions:

• chr10-71698431-A-C
• chr10-71698431-A-G
• chr10-71698431-A-T

Variant summary

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

The NM_022124.6(CDH23):​c.2397+2906A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 151,888 control chromosomes in the GnomAD database, including 35,871 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 0.68 (35871 hom., cov: 30)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH23	NM_022124.6	c.2397+2906A>C		intron_variant		ENST00000224721.12
CDH23	NM_001171930.2	c.2397+2906A>C		intron_variant
CDH23	NM_001171931.2	c.2397+2906A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12	c.2397+2906A>C		intron_variant		5	NM_022124.6	P1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102858 AN: 151772 Hom.: 35856 Cov.: 30

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.678 AC: 102907 AN: 151888 Hom.: 35871 Cov.: 30 AF XY: 0.674 AC XY: 50058 AN XY: 74224

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.688

Alfa AF: 0.753 Hom.: 56343

Bravo AF: 0.665

Asia WGS AF: 0.676 AC: 2352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.45

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: rs1234888; hg19: chr10-73458188;