16-68732910-C-T

Variant names:

• chr16-68732910-C-T
• rs9940250
• XM_047433450.1:c.*887C>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.*887C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 149,800 control chromosomes in the GnomAD database, including 49,371 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 (49371 hom., cov: 23)
• Consequence: CDH3 XM_047433450.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH3	XM_047433450.1	c.*887C>T		3_prime_UTR_variant	Exon 17 of 17		XP_047289406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.806 AC: 120643 AN: 149684 Hom.: 49365 Cov.: 23

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.926

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.930

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.847

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.806 AC: 120687 AN: 149800 Hom.: 49371 Cov.: 23 AF XY: 0.800 AC XY: 58384 AN XY: 72942

African (AFR) AF: 0.663 AC: 26893 AN: 40534

American (AMR) AF: 0.799 AC: 11901 AN: 14900

Ashkenazi Jewish (ASJ) AF: 0.930 AC: 3220 AN: 3462

East Asian (EAS) AF: 0.755 AC: 3759 AN: 4980

South Asian (SAS) AF: 0.783 AC: 3676 AN: 4694

European-Finnish (FIN) AF: 0.824 AC: 8464 AN: 10270

Middle Eastern (MID) AF: 0.846 AC: 247 AN: 292

European-Non Finnish (NFE) AF: 0.886 AC: 59973 AN: 67688

Other (OTH) AF: 0.827 AC: 1719 AN: 2078

Alfa AF: 0.832 Hom.: 6503

Bravo AF: 0.796

Asia WGS AF: 0.768 AC: 2672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.57
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs9940250; hg19: chr16-68766813;