rs111033474
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_022124.6(CDH23):c.894G>A(p.Leu298=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000898 in 1,613,962 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0050 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00047 ( 9 hom. )
Consequence
CDH23
NM_022124.6 synonymous
NM_022124.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.145
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant 10-71615565-G-A is Benign according to our data. Variant chr10-71615565-G-A is described in ClinVar as [Benign]. Clinvar id is 46060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.145 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00502 (765/152262) while in subpopulation AFR AF= 0.0177 (737/41554). AF 95% confidence interval is 0.0167. There are 6 homozygotes in gnomad4. There are 351 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 6 AD,AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.894G>A | p.Leu298= | synonymous_variant | 10/70 | ENST00000224721.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.894G>A | p.Leu298= | synonymous_variant | 10/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00501 AC: 762AN: 152144Hom.: 6 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
762
AN:
152144
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00118 AC: 293AN: 249264Hom.: 4 AF XY: 0.000873 AC XY: 118AN XY: 135230
GnomAD3 exomes
AF:
AC:
293
AN:
249264
Hom.:
AF XY:
AC XY:
118
AN XY:
135230
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000469 AC: 685AN: 1461700Hom.: 9 Cov.: 32 AF XY: 0.000437 AC XY: 318AN XY: 727136
GnomAD4 exome
AF:
AC:
685
AN:
1461700
Hom.:
Cov.:
32
AF XY:
AC XY:
318
AN XY:
727136
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00502 AC: 765AN: 152262Hom.: 6 Cov.: 32 AF XY: 0.00471 AC XY: 351AN XY: 74446
GnomAD4 genome
?
AF:
AC:
765
AN:
152262
Hom.:
Cov.:
32
AF XY:
AC XY:
351
AN XY:
74446
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
3
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 25, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 01, 2013 | Leu298Leu in exon 10 of CDH23: This variant is not expected to have clinical sig nificance because it has been identified in 1.5% (59/4050) of African American c hromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/E VS/; dbSNP rs111033474). In addition, it does not alter an amino acid residue an d is not near a splice junction. - |
Usher syndrome type 1 Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 06, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at