chr10-71509929-C-A

Variant names:

• chr10-71509929-C-A
• rs115584464
• NM_022124.6:c.146-153C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_022124.6(CDH23):​c.146-153C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 756,456 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (18 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00200
• Publications: 1 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=-0.87).
• BP6: Variant 10-71509929-C-A is Benign according to our data. Variant chr10-71509929-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1212501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.013 (1979/152270) while in subpopulation AFR AF = 0.041 (1702/41540). AF 95% confidence interval is 0.0394. There are 40 homozygotes in GnomAd4. There are 992 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 40 AR gene

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.146-153C>A		intron	N/A	NP_071407.4
	CDH23	NM_001171930.2		c.146-153C>A		intron	N/A	NP_001165401.1	A0A087WYR8
	CDH23	NM_001171931.2		c.146-153C>A		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.146-153C>A		intron	N/A	ENSP00000224721.9	Q9H251-1
	CDH23	ENST00000616684.4	TSL:5	c.146-153C>A		intron	N/A	ENSP00000482036.2	A0A087WYR8
	CDH23	ENST00000398809.9	TSL:5	c.146-153C>A		intron	N/A	ENSP00000381789.5	A0A0A0MS94

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1970 AN: 152152 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00714

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00245 AC: 1480 AN: 604186 Hom.: 18 Cov.: 8 AF XY: 0.00223 AC XY: 700 AN XY: 314486

African (AFR) AF: 0.0383 AC: 642 AN: 16780

American (AMR) AF: 0.00314 AC: 93 AN: 29608

Ashkenazi Jewish (ASJ) AF: 0.0162 AC: 265 AN: 16380

East Asian (EAS) AF: 0.00 AC: 0 AN: 32606

South Asian (SAS) AF: 0.000316 AC: 17 AN: 53878

European-Finnish (FIN) AF: 0.0000288 AC: 1 AN: 34680

Middle Eastern (MID) AF: 0.00430 AC: 15 AN: 3490

European-Non Finnish (NFE) AF: 0.000730 AC: 281 AN: 385186

Other (OTH) AF: 0.00526 AC: 166 AN: 31578

GnomAD4 genome AF: 0.0130 AC: 1979 AN: 152270 Hom.: 40 Cov.: 32 AF XY: 0.0133 AC XY: 992 AN XY: 74452

African (AFR) AF: 0.0410 AC: 1702 AN: 41540

American (AMR) AF: 0.00713 AC: 109 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0230 AC: 80 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68014

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.0130 Hom.: 3

Bravo AF: 0.0148

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.78
DANN	Benign	0.73
PhyloP100		0.0020
Mutation Taster		=100/0	polymorphism

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: rs115584464; hg19: chr10-73269686;