10-71541584-A-G

Position:

• chr10-71541584-A-G

Variant summary

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

The NM_022124.6(CDH23):​c.430-25158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,222 control chromosomes in the GnomAD database, including 41,113 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 0.73 (41113 hom., cov: 33)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.78

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH23	NM_022124.6	c.430-25158A>G		intron_variant		ENST00000224721.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12	c.430-25158A>G		intron_variant		5	NM_022124.6	P1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110806 AN: 152104 Hom.: 41063 Cov.: 33

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.729 AC: 110910 AN: 152222 Hom.: 41113 Cov.: 33 AF XY: 0.731 AC XY: 54366 AN XY: 74390

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.726

Alfa AF: 0.681 Hom.: 19151

Bravo AF: 0.726

Asia WGS AF: 0.800 AC: 2781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.27

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: rs2394807; hg19: chr10-73301341;