rs7084874

Positions:

• chr10-71754607-G-A
• chr10-71754607-G-C
• chr10-71754607-G-T

Variant summary

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

The ENST00000394957.8(VSIR):​c.676+752C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,030 control chromosomes in the GnomAD database, including 4,111 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 0.22 (4111 hom., cov: 32)
• Consequence: VSIR ENST00000394957.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6	c.4845+12686G>A		intron_variant		ENST00000224721.12	NP_071407.4
VSIR	NM_022153.2	c.676+752C>T		intron_variant		ENST00000394957.8	NP_071436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.4845+12686G>A		intron_variant		5	NM_022124.6	ENSP00000224721	P1
VSIR	ENST00000394957.8	c.676+752C>T		intron_variant		1	NM_022153.2	ENSP00000378409	P1
VSIR	ENST00000470317.2	n.161+752C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34086 AN: 151912 Hom.: 4110 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.224 AC: 34090 AN: 152030 Hom.: 4111 Cov.: 32 AF XY: 0.223 AC XY: 16590 AN XY: 74296

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.213

Alfa AF: 0.262 Hom.: 5638

Bravo AF: 0.216

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.8
DANN	Benign	0.79

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: rs7084874; hg19: chr10-73514364;