rs6499188

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH3	ENST00000565453.1	n.223-4124G>A		intron_variant		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

Gnomad4 AFR AF: 0.753

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.742

Alfa AF: 0.749 Hom.: 71083

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6499188; hg19: chr16-68674788;