ENST00000569080.2:c.*46-1835A>G

Variant names:

• chr16-68725318-A-G
• rs4783566
• ENST00000569080.2:c.*46-1835A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

CDH3 Gene-Disease associations (from GenCC):

• EEM syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital hypotrichosis with juvenile macular dystrophy

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDH3	XM_011522800.4	c.*46-1835A>G		intron_variant	Intron 16 of 16		XP_011521102.1
CDH3	XM_047433450.1	c.*45+2702A>G		intron_variant	Intron 16 of 16		XP_047289406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH3	ENST00000569080.2	c.*46-1835A>G		intron_variant	Intron 2 of 2	5		ENSP00000463415.1

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

African (AFR) AF: 0.840 AC: 34761 AN: 41370

American (AMR) AF: 0.819 AC: 12472 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.930 AC: 3222 AN: 3464

East Asian (EAS) AF: 0.771 AC: 3939 AN: 5108

South Asian (SAS) AF: 0.785 AC: 3769 AN: 4800

European-Finnish (FIN) AF: 0.824 AC: 8641 AN: 10484

Middle Eastern (MID) AF: 0.860 AC: 251 AN: 292

European-Non Finnish (NFE) AF: 0.888 AC: 60157 AN: 67782

Other (OTH) AF: 0.870 AC: 1829 AN: 2102

Alfa AF: 0.859 Hom.: 9755

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
PhyloP100		-0.32

Splicing

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

Other links and lift over

dbSNP: rs4783566; hg19: chr16-68759221;