16-68730609-C-T

Variant names:

• chr16-68730609-C-T
• rs9989407
• XM_047433450.1:c.*46-1460C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047433450.1(CDH3):​c.*46-1460C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,168 control chromosomes in the GnomAD database, including 50,154 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 0.81 (50154 hom., cov: 33)
• Consequence: CDH3 XM_047433450.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 10 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, ClinGen
• congenital hypotrichosis with juvenile macular dystrophy

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122557 AN: 152050 Hom.: 50147 Cov.: 33

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.930

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.806 AC: 122602 AN: 152168 Hom.: 50154 Cov.: 33 AF XY: 0.801 AC XY: 59596 AN XY: 74410

African (AFR) AF: 0.664 AC: 27530 AN: 41472

American (AMR) AF: 0.799 AC: 12214 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.930 AC: 3229 AN: 3472

East Asian (EAS) AF: 0.774 AC: 4003 AN: 5174

South Asian (SAS) AF: 0.785 AC: 3788 AN: 4828

European-Finnish (FIN) AF: 0.825 AC: 8745 AN: 10598

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.886 AC: 60258 AN: 68024

Other (OTH) AF: 0.828 AC: 1744 AN: 2106

Alfa AF: 0.830 Hom.: 8501

Bravo AF: 0.797

Asia WGS AF: 0.774 AC: 2693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.12
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs9989407; hg19: chr16-68764512;