rs1234888

Variant names:

• chr10-71698431-A-C
• rs1234888
• NM_022124.6:c.2397+2906A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-71698431-A-C
• chr10-71698431-A-G
• chr10-71698431-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022124.6(CDH23):​c.2397+2906A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 151,888 control chromosomes in the GnomAD database, including 35,871 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 0.68 (35871 hom., cov: 30)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 4 publications found

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]

CDH23 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 12

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Usher syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Usher syndrome type 1D

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.2397+2906A>C		intron_variant	Intron 22 of 69	ENST00000224721.12	NP_071407.4
CDH23	NM_001171930.2	c.2397+2906A>C		intron_variant	Intron 22 of 31		NP_001165401.1
CDH23	NM_001171931.2	c.2397+2906A>C		intron_variant	Intron 22 of 25		NP_001165402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.2397+2906A>C		intron_variant	Intron 22 of 69	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes AF: 0.678 AC: 102858 AN: 151772 Hom.: 35856 Cov.: 30

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.678 AC: 102907 AN: 151888 Hom.: 35871 Cov.: 30 AF XY: 0.674 AC XY: 50058 AN XY: 74224

African (AFR) AF: 0.514 AC: 21290 AN: 41390

American (AMR) AF: 0.616 AC: 9400 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2788 AN: 3472

East Asian (EAS) AF: 0.631 AC: 3252 AN: 5154

South Asian (SAS) AF: 0.755 AC: 3623 AN: 4800

European-Finnish (FIN) AF: 0.708 AC: 7476 AN: 10560

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52723 AN: 67936

Other (OTH) AF: 0.688 AC: 1452 AN: 2110

Alfa AF: 0.741 Hom.: 76983

Bravo AF: 0.665

Asia WGS AF: 0.676 AC: 2352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.45
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1234888; hg19: chr10-73458188;