chr10-71511238-A-G

Variant names:

• chr10-71511238-A-G
• rs3802718
• NM_022124.6:c.429+26A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022124.6(CDH23):​c.429+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,601,118 control chromosomes in the GnomAD database, including 363,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41854 hom., cov: 33)
  • Exomes 𝑓: 0.66 (321965 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.23
• Publications: 11 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-AS1 (HGNC:31433): (CDH23 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-71511238-A-G is Benign according to our data. Variant chr10-71511238-A-G is described in ClinVar as Benign. ClinVar VariationId is 261548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022124.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	NM_022124.6	MANE Select	c.429+26A>G		intron	N/A	NP_071407.4
	CDH23	NM_001171930.2		c.429+26A>G		intron	N/A	NP_001165401.1	A0A087WYR8
	CDH23	NM_001171931.2		c.429+26A>G		intron	N/A	NP_001165402.1	Q8N5B3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	ENST00000224721.12	TSL:5 MANE Select	c.429+26A>G		intron	N/A	ENSP00000224721.9	Q9H251-1
	CDH23	ENST00000616684.4	TSL:5	c.429+26A>G		intron	N/A	ENSP00000482036.2	A0A087WYR8
	CDH23	ENST00000398809.9	TSL:5	c.429+26A>G		intron	N/A	ENSP00000381789.5	A0A0A0MS94

Frequencies

GnomAD3 genomes AF: 0.731 AC: 110878 AN: 151734 Hom.: 41808 Cov.: 33

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.699

GnomAD2 exomes AF: 0.660 AC: 164324 AN: 248910 AF XY: 0.659

Gnomad AFR exome AF: 0.930

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.733

Gnomad EAS exome AF: 0.778

Gnomad FIN exome AF: 0.733

Gnomad NFE exome AF: 0.662

Gnomad OTH exome AF: 0.659

GnomAD4 exome AF: 0.663 AC: 961402 AN: 1449264 Hom.: 321965 Cov.: 29 AF XY: 0.662 AC XY: 477697 AN XY: 721822

African (AFR) AF: 0.934 AC: 31054 AN: 33236

American (AMR) AF: 0.467 AC: 20885 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 18957 AN: 26044

East Asian (EAS) AF: 0.758 AC: 30052 AN: 39636

South Asian (SAS) AF: 0.606 AC: 52154 AN: 85994

European-Finnish (FIN) AF: 0.726 AC: 38654 AN: 53266

Middle Eastern (MID) AF: 0.700 AC: 4021 AN: 5748

European-Non Finnish (NFE) AF: 0.658 AC: 724702 AN: 1100696

Other (OTH) AF: 0.683 AC: 40923 AN: 59948

GnomAD4 genome AF: 0.731 AC: 110976 AN: 151854 Hom.: 41854 Cov.: 33 AF XY: 0.730 AC XY: 54194 AN XY: 74202

African (AFR) AF: 0.920 AC: 38165 AN: 41468

American (AMR) AF: 0.577 AC: 8810 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2547 AN: 3468

East Asian (EAS) AF: 0.777 AC: 4006 AN: 5156

South Asian (SAS) AF: 0.597 AC: 2872 AN: 4814

European-Finnish (FIN) AF: 0.746 AC: 7839 AN: 10510

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.658 AC: 44634 AN: 67854

Other (OTH) AF: 0.695 AC: 1468 AN: 2112

Alfa AF: 0.701 Hom.: 9594

Bravo AF: 0.724

Asia WGS AF: 0.681 AC: 2370 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal recessive nonsyndromic hearing loss 12 (1)
-	-	1	not specified (1)
-	-	1	Usher syndrome type 1D (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.48
PhyloP100		-1.2
PromoterAI		-0.0033	Neutral
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: rs3802718; hg19: chr10-73270995;