rs4925325

Positions:

• chr20-61939168-G-A

Variant summary

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

The NM_001794.5(CDH4):​c.*2225G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,220 control chromosomes in the GnomAD database, including 4,214 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 0.23 (4214 hom., cov: 33)
  • Exomes 𝑓: 0.19 (0 hom.)
• Consequence: CDH4 NM_001794.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

Genes affected

CDH4 (HGNC:1763): (cadherin 4) This gene is a classical cadherin from the cadherin superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Based on studies in chicken and mouse, this cadherin is thought to play an important role during brain segmentation and neuronal outgrowth. In addition, a role in kidney and muscle development is indicated. Of particular interest are studies showing stable cis-heterodimers of cadherins 2 and 4 in cotransfected cell lines. Previously thought to interact in an exclusively homophilic manner, this is the first evidence of cadherin heterodimerization. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH4	NM_001794.5	c.*2225G>A		3_prime_UTR_variant	16/16	ENST00000614565.5	NP_001785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH4	ENST00000614565.5	c.*2225G>A		3_prime_UTR_variant	16/16	1	NM_001794.5	ENSP00000484928.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34361 AN: 152062 Hom.: 4202 Cov.: 33

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.190 AC: 8 AN: 42 Hom.: 0 Cov.: 0 AF XY: 0.233 AC XY: 7 AN XY: 30

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.226 AC: 34398 AN: 152178 Hom.: 4214 Cov.: 33 AF XY: 0.229 AC XY: 17049 AN XY: 74396

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.223

Alfa AF: 0.235 Hom.: 5535

Bravo AF: 0.230

Asia WGS AF: 0.325 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.58

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: rs4925325; hg19: chr20-60514224;