rs6499188

Variant names:

• chr16-68640885-G-A
• rs6499188
• ENST00000565453.1:n.223-4124G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-68640885-G-A
• chr16-68640885-G-C

Variant summary

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

The ENST00000565453.1(CDH3):​n.223-4124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 150,756 control chromosomes in the GnomAD database, including 42,925 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 0.75 (42925 hom., cov: 26)
• Consequence: CDH3 ENST00000565453.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 38 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH3	ENST00000565453.1	n.223-4124G>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.753 AC: 113501 AN: 150638 Hom.: 42876 Cov.: 26

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.754 AC: 113608 AN: 150756 Hom.: 42925 Cov.: 26 AF XY: 0.755 AC XY: 55462 AN XY: 73494

African (AFR) AF: 0.753 AC: 30854 AN: 40948

American (AMR) AF: 0.719 AC: 10879 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2374 AN: 3458

East Asian (EAS) AF: 0.788 AC: 3994 AN: 5068

South Asian (SAS) AF: 0.765 AC: 3642 AN: 4762

European-Finnish (FIN) AF: 0.795 AC: 8105 AN: 10198

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51183 AN: 67874

Other (OTH) AF: 0.742 AC: 1562 AN: 2106

Alfa AF: 0.750 Hom.: 162615

Bravo AF: 0.749

Asia WGS AF: 0.716 AC: 2492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.25
PhyloP100		-0.42

Splicing

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

Other links and lift over

dbSNP: rs6499188; hg19: chr16-68674788;