rs1867982

chr10-71767290-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022124.6(CDH23):c.4846-10390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,240 control chromosomes in the GnomAD database, including 61,604 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 0.90 (61604 hom., cov: 34)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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]

VSIR (HGNC:30085): (V-set immunoregulatory receptor) Enables endopeptidase activator activity; enzyme binding activity; and identical protein binding activity. Involved in several processes, including negative regulation of cytokine production; positive regulation of macromolecule metabolic process; and regulation of T cell activation. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH23	NM_022124.6	c.4846-10390A>G		intron_variant		ENST00000224721.12
VSIR	NM_022153.2	c.83-5264T>C		intron_variant		ENST00000394957.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12	c.4846-10390A>G		intron_variant		5	NM_022124.6	P1
VSIR	ENST00000394957.8	c.83-5264T>C		intron_variant		1	NM_022153.2	P1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136561 AN: 152122 Hom.: 61561 Cov.: 34

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.898 AC: 136654 AN: 152240 Hom.: 61604 Cov.: 34 AF XY: 0.893 AC XY: 66431 AN XY: 74424

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.893

Gnomad4 OTH AF: 0.899

Alfa AF: 0.895 Hom.: 54476

Bravo AF: 0.899

Asia WGS AF: 0.800 AC: 2783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.051
Dann	Benign	0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs1867982; hg19: chr10-73527047;