rs73275848

Variant names:

• chr10-71730457-C-T
• rs73275848
• NM_022124.6:c.3580-12C>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.3580-12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00924 in 1,612,894 control chromosomes in the GnomAD database, including 1,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (615 hom., cov: 33)
  • Exomes 𝑓: 0.0051 (590 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Scores: Splicing: ADA: 0.00002238
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.65
• 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]

C10orf105 (HGNC:20304): (chromosome 10 open reading frame 105) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-71730457-C-T is Benign according to our data. Variant chr10-71730457-C-T is described in ClinVar as Benign. ClinVar VariationId is 45924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	NM_022124.6	MANE Select	c.3580-12C>T		intron	N/A	NP_071407.4
	CDH23	NM_001171930.2		c.3580-12C>T		intron	N/A	NP_001165401.1
	C10orf105	NM_001168390.2		c.-6+7271G>A		intron	N/A	NP_001161862.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	ENST00000224721.12	TSL:5 MANE Select	c.3580-12C>T		intron	N/A	ENSP00000224721.9
	CDH23	ENST00000616684.4	TSL:5	c.3580-12C>T		intron	N/A	ENSP00000482036.2
	CDH23	ENST00000398809.9	TSL:5	c.3577-12C>T		intron	N/A	ENSP00000381789.5

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7460 AN: 152114 Hom.: 616 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0354

GnomAD2 exomes AF: 0.0121 AC: 2996 AN: 247868 AF XY: 0.00915

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.00842

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000512

Gnomad NFE exome AF: 0.000687

Gnomad OTH exome AF: 0.00631

GnomAD4 exome AF: 0.00509 AC: 7435 AN: 1460664 Hom.: 590 Cov.: 31 AF XY: 0.00436 AC XY: 3166 AN XY: 726572

African (AFR) AF: 0.174 AC: 5823 AN: 33444

American (AMR) AF: 0.00978 AC: 437 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000638 AC: 55 AN: 86176

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53320

Middle Eastern (MID) AF: 0.00771 AC: 41 AN: 5320

European-Non Finnish (NFE) AF: 0.000338 AC: 376 AN: 1111610

Other (OTH) AF: 0.0114 AC: 687 AN: 60304

GnomAD4 genome AF: 0.0491 AC: 7470 AN: 152230 Hom.: 615 Cov.: 33 AF XY: 0.0470 AC XY: 3500 AN XY: 74442

African (AFR) AF: 0.169 AC: 7026 AN: 41508

American (AMR) AF: 0.0209 AC: 319 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68022

Other (OTH) AF: 0.0350 AC: 74 AN: 2114

Alfa AF: 0.0424 Hom.: 93

Bravo AF: 0.0563

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.14
DANN	Benign	0.82
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
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: rs73275848; hg19: chr10-73490214;