rs1867982

Variant names:

• chr10-71767290-A-G
• rs1867982
• NM_022124.6:c.4846-10390A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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]

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.4846-10390A>G		intron_variant	Intron 38 of 69	ENST00000224721.12	NP_071407.4
VSIR	NM_022153.2	c.83-5264T>C		intron_variant	Intron 1 of 6	ENST00000394957.8	NP_071436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.4846-10390A>G		intron_variant	Intron 38 of 69	5	NM_022124.6	ENSP00000224721.9
VSIR	ENST00000394957.8	c.83-5264T>C		intron_variant	Intron 1 of 6	1	NM_022153.2	ENSP00000378409.3

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

African (AFR) AF: 0.968 AC: 40220 AN: 41542

American (AMR) AF: 0.823 AC: 12578 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3252 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3910 AN: 5172

South Asian (SAS) AF: 0.914 AC: 4415 AN: 4832

European-Finnish (FIN) AF: 0.816 AC: 8654 AN: 10600

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60715 AN: 68008

Other (OTH) AF: 0.899 AC: 1903 AN: 2116

Alfa AF: 0.893 Hom.: 106623

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
PhyloP100		-2.4
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: rs1867982; hg19: chr10-73527047;