chr10-71803088-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_022124.6(CDH23):​c.7660+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,605,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

CDH23
NM_022124.6 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 10-71803088-C-T is Benign according to our data. Variant chr10-71803088-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 162944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDH23NM_022124.6 linkuse as main transcriptc.7660+13C>T intron_variant ENST00000224721.12
CDH23NM_001171933.1 linkuse as main transcriptc.940+13C>T intron_variant
CDH23NM_001171934.1 linkuse as main transcriptc.940+13C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDH23ENST00000224721.12 linkuse as main transcriptc.7660+13C>T intron_variant 5 NM_022124.6 P1Q9H251-1

Frequencies

GnomAD3 genomes
AF:
0.000867
AC:
132
AN:
152204
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00309
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000284
AC:
70
AN:
246360
Hom.:
0
AF XY:
0.000202
AC XY:
27
AN XY:
133536
show subpopulations
Gnomad AFR exome
AF:
0.00439
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000897
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000847
AC:
123
AN:
1452678
Hom.:
0
Cov.:
40
AF XY:
0.0000527
AC XY:
38
AN XY:
720846
show subpopulations
Gnomad4 AFR exome
AF:
0.00330
Gnomad4 AMR exome
AF:
0.0000450
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.000134
GnomAD4 genome
AF:
0.000867
AC:
132
AN:
152322
Hom.:
0
Cov.:
31
AF XY:
0.000846
AC XY:
63
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00308
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000925
Hom.:
0
Bravo
AF:
0.00108

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 25, 2024- -
Likely benign, criteria provided, single submitterclinical testingGeneDxNov 24, 2021See Variant Classification Assertion Criteria. -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineOct 25, 20167660+13C>T in Intron 54 of CDH23: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 0.4% (40/9782) of African chromosomes by the Ex ome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs374011 250). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
6.3
DANN
Benign
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs374011250; hg19: chr10-73562845; API