rs3785133

Positions:

• chr16-68694708-G-A
• chr16-68694708-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001793.6(CDH3):​c.2003-547G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,748 control chromosomes in the GnomAD database, including 24,427 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 0.56 (24427 hom., cov: 31)
• Consequence: CDH3 NM_001793.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH3	NM_001793.6	c.2003-547G>A		intron_variant		ENST00000264012.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH3	ENST00000264012.9	c.2003-547G>A		intron_variant		1	NM_001793.6	P1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85546 AN: 151632 Hom.: 24424 Cov.: 31

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.564 AC: 85589 AN: 151748 Hom.: 24427 Cov.: 31 AF XY: 0.560 AC XY: 41498 AN XY: 74120

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.571

Alfa AF: 0.584 Hom.: 6513

Bravo AF: 0.554

Asia WGS AF: 0.493 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.32
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs3785133; hg19: chr16-68728611;