rs7087735

chr10-71567000-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022124.6(CDH23):c.624+64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,490,842 control chromosomes in the GnomAD database, including 94,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9779 hom., cov: 32)
  • Exomes 𝑓: 0.35 (84548 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.68

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-71567000-C-T is Benign according to our data. Variant chr10-71567000-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1177610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71567000-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH23	NM_022124.6	c.624+64C>T		intron_variant		ENST00000224721.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12	c.624+64C>T		intron_variant		5	NM_022124.6	P1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53679 AN: 151876 Hom.: 9773 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.353 AC: 472155 AN: 1338848 Hom.: 84548 AF XY: 0.353 AC XY: 234915 AN XY: 666138

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.544

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.353 AC: 53707 AN: 151994 Hom.: 9779 Cov.: 32 AF XY: 0.352 AC XY: 26136 AN XY: 74290

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.325

Alfa AF: 0.341 Hom.: 1816

Bravo AF: 0.357

Asia WGS AF: 0.474 AC: 1647 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Pituitary adenoma 5, multiple types Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Usher syndrome type 1D Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Autosomal recessive nonsyndromic hearing loss 12 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.53
Dann	Benign	0.55

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: rs7087735; hg19: chr10-73326757;