rs4783566

chr16-68725318-A-G

Variant summary

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

The ENST00000569080.2(CDH3):c.*46-1835A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 151,542 control chromosomes in the GnomAD database, including 55,833 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 0.86 (55833 hom., cov: 30)
• Consequence: CDH3 ENST00000569080.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

Genes affected

CDH3 (HGNC:1762): (cadherin 3) This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. In addition, aberrant expression of this protein is observed in cervical adenocarcinomas. Mutations in this gene are associated with hypotrichosis with juvenile macular dystrophy and ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome (EEMS). [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH3	XM_011522800.4	c.*46-1835A>G		intron_variant
CDH3	XM_047433450.1	c.*45+2702A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH3	ENST00000569080.2	c.*46-1835A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.857 AC: 129799 AN: 151422 Hom.: 55805 Cov.: 30

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.930

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.866

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.874

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

GnomAD4 genome AF: 0.857 AC: 129882 AN: 151542 Hom.: 55833 Cov.: 30 AF XY: 0.851 AC XY: 63001 AN XY: 74018

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.819

Gnomad4 ASJ AF: 0.930

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.870

Alfa AF: 0.860 Hom.: 9499

Bravo AF: 0.855

Asia WGS AF: 0.792 AC: 2753 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.3
Dann	Benign	0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4783566; hg19: chr16-68759221;