16-68686994-A-G

Variant names:

• chr16-68686994-A-G
• rs3114403
• NM_001793.6:c.1571-518A>G

Variant summary

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

The NM_001793.6(CDH3):​c.1571-518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,228 control chromosomes in the GnomAD database, including 61,351 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 0.90 (61351 hom., cov: 31)
• Consequence: CDH3 NM_001793.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780
• Publications: 11 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001793.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH3	NM_001793.6	MANE Select	c.1571-518A>G		intron	N/A	NP_001784.2
	CDH3	NM_001317195.3		c.1571-518A>G		intron	N/A	NP_001304124.1
	CDH3	NM_001317196.2		c.1406-518A>G		intron	N/A	NP_001304125.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH3	ENST00000264012.9	TSL:1 MANE Select	c.1571-518A>G		intron	N/A	ENSP00000264012.4
	CDH3	ENST00000429102.6	TSL:1	c.1571-518A>G		intron	N/A	ENSP00000398485.2
	CDH3	ENST00000542274.5	TSL:2	n.*1309-518A>G		intron	N/A	ENSP00000464021.1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136177 AN: 152110 Hom.: 61299 Cov.: 31

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.895 AC: 136284 AN: 152228 Hom.: 61351 Cov.: 31 AF XY: 0.888 AC XY: 66096 AN XY: 74410

African (AFR) AF: 0.978 AC: 40664 AN: 41570

American (AMR) AF: 0.832 AC: 12721 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3215 AN: 3472

East Asian (EAS) AF: 0.774 AC: 3997 AN: 5162

South Asian (SAS) AF: 0.788 AC: 3792 AN: 4814

European-Finnish (FIN) AF: 0.815 AC: 8629 AN: 10590

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60307 AN: 68016

Other (OTH) AF: 0.886 AC: 1875 AN: 2116

Alfa AF: 0.916 Hom.: 13210

Bravo AF: 0.898

Asia WGS AF: 0.806 AC: 2807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	10
DANN	Benign	0.51
PhyloP100		0.078
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3114403; hg19: chr16-68720897;