rs8049247

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001793.6(CDH3):c.612C>A(p.Ile204Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,613,738 control chromosomes in the GnomAD database, including 17,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2695 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14714 hom. )

Consequence

CDH3
NM_001793.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -8.82

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 16-68678827-C-A is Benign according to our data. Variant chr16-68678827-C-A is described in ClinVar as [Benign]. Clinvar id is 320227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.82 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH3	NM_001793.6 link	c.612C>A	p.Ile204Ile	synonymous_variant	Exon 6 of 16	ENST00000264012.9	NP_001784.2	P22223-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH3	ENST00000264012.9 link	c.612C>A	p.Ile204Ile	synonymous_variant	Exon 6 of 16	1	NM_001793.6	ENSP00000264012.4		P22223-1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26292

AN:

151992

Hom.:

2694

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0774

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.168

GnomAD3 exomes

AF:

0.126

AC:

31744

AN:

251260

Hom.:

2545

AF XY:

0.124

AC XY:

16842

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.0730

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.00125

Gnomad SAS exome

AF:

0.0760

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.135

AC:

197528

AN:

1461628

Hom.:

14714

Cov.:

AF XY:

0.133

AC XY:

96961

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.296

Gnomad4 AMR exome

AF:

0.0780

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.0757

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.173

AC:

26328

AN:

152110

Hom.:

2695

Cov.:

AF XY:

0.169

AC XY:

12594

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.287

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0774

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.143

Gnomad4 OTH

AF:

0.168

Alfa

AF:

0.139

Hom.:

2844

Bravo

AF:

0.174

Asia WGS

AF:

0.0610

AC:

213

AN:

3478

EpiCase

AF:

0.143

EpiControl

AF:

0.143

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

EEM syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

2.6

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over