rs16958232

Variant names:

• chr16-68647480-A-G
• rs16958232
• NM_001793.6:c.160+1730A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001793.6(CDH3):​c.160+1730A>G variant causes a intron change. The variant allele was found at a frequency of 0.0679 in 152,132 control chromosomes in the GnomAD database, including 883 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 0.068 (883 hom., cov: 31)
• Consequence: CDH3 NM_001793.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH3	NM_001793.6	MANE Select	c.160+1730A>G		intron	N/A	NP_001784.2
	CDH3	NM_001317195.3		c.160+1730A>G		intron	N/A	NP_001304124.1	P22223-2
	CDH3	NM_001317196.2		c.-6+2056A>G		intron	N/A	NP_001304125.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH3	ENST00000264012.9	TSL:1 MANE Select	c.160+1730A>G		intron	N/A	ENSP00000264012.4	P22223-1
	CDH3	ENST00000429102.6	TSL:1	c.160+1730A>G		intron	N/A	ENSP00000398485.2	P22223-2
	CDH3	ENST00000914963.1		c.160+1730A>G		intron	N/A	ENSP00000585022.1

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10298 AN: 152014 Hom.: 879 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.0607

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

GnomAD4 genome AF: 0.0679 AC: 10324 AN: 152132 Hom.: 883 Cov.: 31 AF XY: 0.0649 AC XY: 4830 AN XY: 74386

African (AFR) AF: 0.199 AC: 8260 AN: 41448

American (AMR) AF: 0.0393 AC: 601 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 74 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4810

European-Finnish (FIN) AF: 0.00509 AC: 54 AN: 10612

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0169 AC: 1150 AN: 68002

Other (OTH) AF: 0.0596 AC: 126 AN: 2114

Alfa AF: 0.0366 Hom.: 118

Bravo AF: 0.0769

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.79
PhyloP100		4.0
Mutation Taster		=99/1	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: rs16958232; hg19: chr16-68681383;