rs537339409

Variant names:

• chr16-68645239-C-G
• rs537339409
• ENST00000429102.6:c.-141C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-68645239-C-G
• chr16-68645239-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The ENST00000429102.6(CDH3):​c.-141C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000789 in 805,832 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00084 (0 hom.)
• Consequence: CDH3 ENST00000429102.6 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0110
• Publications: 0 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-AS1 (HGNC:56084): (CDH3 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000578 (88/152314) while in subpopulation NFE AF = 0.00109 (74/68020). AF 95% confidence interval is 0.000888. There are 1 homozygotes in GnomAd4. There are 39 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429102.6. 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-AS1	NR_186394.1		n.724G>C		non_coding_transcript_exon	Exon 2 of 2
	CDH3	NM_001793.6	MANE Select	c.-141C>G		upstream_gene	N/A	NP_001784.2
	CDH3	NM_001317195.3		c.-141C>G		upstream_gene	N/A	NP_001304124.1	P22223-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH3	ENST00000429102.6	TSL:1	c.-141C>G		5_prime_UTR	Exon 1 of 16	ENSP00000398485.2	P22223-2
	CDH3-AS1	ENST00000562172.2	TSL:3	n.691G>C		non_coding_transcript_exon	Exon 2 of 2
	CDH3	ENST00000565453.1	TSL:4	n.453C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.000578 AC: 88 AN: 152196 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000839 AC: 548 AN: 653518 Hom.: 0 Cov.: 9 AF XY: 0.000897 AC XY: 311 AN XY: 346766

African (AFR) AF: 0.000170 AC: 3 AN: 17648

American (AMR) AF: 0.000202 AC: 7 AN: 34616

Ashkenazi Jewish (ASJ) AF: 0.000696 AC: 14 AN: 20128

East Asian (EAS) AF: 0.00 AC: 0 AN: 32516

South Asian (SAS) AF: 0.0000157 AC: 1 AN: 63826

European-Finnish (FIN) AF: 0.000794 AC: 28 AN: 35286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3914

European-Non Finnish (NFE) AF: 0.00117 AC: 483 AN: 411830

Other (OTH) AF: 0.000356 AC: 12 AN: 33754

GnomAD4 genome AF: 0.000578 AC: 88 AN: 152314 Hom.: 1 Cov.: 33 AF XY: 0.000524 AC XY: 39 AN XY: 74492

African (AFR) AF: 0.0000722 AC: 3 AN: 41578

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000848 AC: 9 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00109 AC: 74 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000318 Hom.: 0

Bravo AF: 0.000544

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	EEM syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		-0.011
PromoterAI		0.00070	Neutral
Mutation Taster		=300/0	polymorphism

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: rs537339409; hg19: chr16-68679142;