rs3802719

Variant names:

• chr10-71511225-G-A
• rs3802719
• NM_022124.6:c.429+13G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-71511225-G-A
• chr10-71511225-G-C
• chr10-71511225-G-T

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+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,610,480 control chromosomes in the GnomAD database, including 364,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41212 hom., cov: 33)
  • Exomes 𝑓: 0.66 (323219 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Scores: Splicing: ADA: 0.00001863
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -2.66
• 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 (REVEL=0.008).
• BP6: Variant 10-71511225-G-A is Benign according to our data. Variant chr10-71511225-G-A is described in ClinVar as Benign. ClinVar VariationId is 45940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 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+13G>A		intron	N/A	NP_071407.4
	CDH23	NM_001171930.2		c.429+13G>A		intron	N/A	NP_001165401.1
	CDH23	NM_001171931.2		c.429+13G>A		intron	N/A	NP_001165402.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	ENST00000224721.12	TSL:5 MANE Select	c.429+13G>A		intron	N/A	ENSP00000224721.9
	CDH23	ENST00000616684.4	TSL:5	c.429+13G>A		intron	N/A	ENSP00000482036.2
	CDH23	ENST00000398809.9	TSL:5	c.429+13G>A		intron	N/A	ENSP00000381789.5

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110146 AN: 151694 Hom.: 41167 Cov.: 33

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.696

GnomAD2 exomes AF: 0.659 AC: 164153 AN: 249118 AF XY: 0.658

Gnomad AFR exome AF: 0.917

Gnomad AMR exome AF: 0.456

Gnomad ASJ exome AF: 0.733

Gnomad EAS exome AF: 0.780

Gnomad FIN exome AF: 0.733

Gnomad NFE exome AF: 0.663

Gnomad OTH exome AF: 0.658

GnomAD4 exome AF: 0.662 AC: 966220 AN: 1458666 Hom.: 323219 Cov.: 35 AF XY: 0.661 AC XY: 479683 AN XY: 725832

African (AFR) AF: 0.921 AC: 30773 AN: 33428

American (AMR) AF: 0.466 AC: 20857 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 19004 AN: 26118

East Asian (EAS) AF: 0.758 AC: 30097 AN: 39694

South Asian (SAS) AF: 0.603 AC: 51942 AN: 86182

European-Finnish (FIN) AF: 0.726 AC: 38723 AN: 53352

Middle Eastern (MID) AF: 0.698 AC: 4022 AN: 5760

European-Non Finnish (NFE) AF: 0.658 AC: 729767 AN: 1109146

Other (OTH) AF: 0.681 AC: 41035 AN: 60270

GnomAD4 genome AF: 0.726 AC: 110241 AN: 151814 Hom.: 41212 Cov.: 33 AF XY: 0.726 AC XY: 53842 AN XY: 74180

African (AFR) AF: 0.905 AC: 37524 AN: 41470

American (AMR) AF: 0.575 AC: 8782 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2544 AN: 3464

East Asian (EAS) AF: 0.778 AC: 4007 AN: 5152

South Asian (SAS) AF: 0.591 AC: 2843 AN: 4814

European-Finnish (FIN) AF: 0.746 AC: 7846 AN: 10516

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.658 AC: 44603 AN: 67824

Other (OTH) AF: 0.693 AC: 1460 AN: 2108

Alfa AF: 0.680 Hom.: 140595

Bravo AF: 0.719

Asia WGS AF: 0.676 AC: 2354 AN: 3478

EpiCase AF: 0.654

EpiControl AF: 0.653

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Autosomal recessive nonsyndromic hearing loss 12 (2)
-	-	2	Usher syndrome type 1D (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.013
DANN	Benign	0.72
PhyloP100		-2.7
PromoterAI		-0.017	Neutral
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0
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: rs3802719; hg19: chr10-73270982; COSMIC: COSV54953394; COSMIC: COSV54953394;