16-68686994-A-G

Variant names:

• chr16-68686994-A-G
• rs3114403
• NM_001793.6:c.1571-518A>G

Variant summary

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

The NM_001793.6(CDH3):​c.1571-518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,228 control chromosomes in the GnomAD database, including 61,351 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 0.90 (61351 hom., cov: 31)
• Consequence: CDH3 NM_001793.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

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 (AFR) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH3	NM_001793.6	c.1571-518A>G		intron_variant	Intron 11 of 15	ENST00000264012.9	NP_001784.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH3	ENST00000264012.9	c.1571-518A>G		intron_variant	Intron 11 of 15	1	NM_001793.6	ENSP00000264012.4
CDH3	ENST00000429102.6	c.1571-518A>G		intron_variant	Intron 11 of 15	1		ENSP00000398485.2
CDH3	ENST00000542274.5	n.*1309-518A>G		intron_variant	Intron 10 of 14	2		ENSP00000464021.1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136177 AN: 152110 Hom.: 61299 Cov.: 31

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.895 AC: 136284 AN: 152228 Hom.: 61351 Cov.: 31 AF XY: 0.888 AC XY: 66096 AN XY: 74410

Gnomad4 AFR AF: 0.978

Gnomad4 AMR AF: 0.832

Gnomad4 ASJ AF: 0.926

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.788

Gnomad4 FIN AF: 0.815

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.886

Alfa AF: 0.868 Hom.: 6024

Bravo AF: 0.898

Asia WGS AF: 0.806 AC: 2807 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	10
DANN	Benign	0.51

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: rs3114403; hg19: chr16-68720897;