rs72817951

chr10-71724016-G-A

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.3370-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 1,552,824 control chromosomes in the GnomAD database, including 3,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (232 hom., cov: 33)
  • Exomes 𝑓: 0.066 (3453 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.37

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]

C10orf105 (HGNC:20304): (chromosome 10 open reading frame 105) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-71724016-G-A is Benign according to our data. Variant chr10-71724016-G-A is described in ClinVar as [Benign]. Clinvar id is 261547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71724016-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH23	NM_022124.6	c.3370-29G>A		intron_variant		ENST00000224721.12
C10orf105	NM_001168390.2	c.-5-7674C>T		intron_variant
CDH23	NM_001171930.2	c.3370-29G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12	c.3370-29G>A		intron_variant		5	NM_022124.6	P1

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7171 AN: 152200 Hom.: 232 Cov.: 33

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0442

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.0681

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.0521

GnomAD3 exomes AF: 0.0441 AC: 6924 AN: 156900 Hom.: 213 AF XY: 0.0429 AC XY: 3564 AN XY: 83058

Gnomad AFR exome AF: 0.0136

Gnomad AMR exome AF: 0.0312

Gnomad ASJ exome AF: 0.0282

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00767

Gnomad FIN exome AF: 0.0656

Gnomad NFE exome AF: 0.0713

Gnomad OTH exome AF: 0.0512

GnomAD4 exome AF: 0.0658 AC: 92142 AN: 1400506 Hom.: 3453 Cov.: 31 AF XY: 0.0639 AC XY: 44177 AN XY: 690910

Gnomad4 AFR exome AF: 0.0106

Gnomad4 AMR exome AF: 0.0337

Gnomad4 ASJ exome AF: 0.0255

Gnomad4 EAS exome AF: 0.0000557

Gnomad4 SAS exome AF: 0.00782

Gnomad4 FIN exome AF: 0.0638

Gnomad4 NFE exome AF: 0.0766

Gnomad4 OTH exome AF: 0.0586

GnomAD4 genome AF: 0.0471 AC: 7169 AN: 152318 Hom.: 232 Cov.: 33 AF XY: 0.0451 AC XY: 3358 AN XY: 74476

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0441

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00849

Gnomad4 FIN AF: 0.0681

Gnomad4 NFE AF: 0.0742

Gnomad4 OTH AF: 0.0510

Alfa AF: 0.0377 Hom.: 28

Bravo AF: 0.0438

Asia WGS AF: 0.00520 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 13, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	9.1
Dann	Benign	0.84

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: rs72817951; hg19: chr10-73483773;