20-61413013-C-T

Variant names:

• chr20-61413013-C-T
• rs1892318
• NM_001794.5:c.169+158076C>T

Variant summary

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

The NM_001794.5(CDH4):​c.169+158076C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,024 control chromosomes in the GnomAD database, including 11,958 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 0.38 (11958 hom., cov: 32)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41
• Publications: 4 publications found

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]

CDH4 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001794.5. 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
	CDH4	NM_001794.5	MANE Select	c.169+158076C>T		intron	N/A	NP_001785.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH4	ENST00000614565.5	TSL:1 MANE Select	c.169+158076C>T		intron	N/A	ENSP00000484928.1	P55283-1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57183 AN: 151906 Hom.: 11959 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.376 AC: 57196 AN: 152024 Hom.: 11958 Cov.: 32 AF XY: 0.376 AC XY: 27919 AN XY: 74294

African (AFR) AF: 0.192 AC: 7955 AN: 41536

American (AMR) AF: 0.353 AC: 5397 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1972 AN: 3472

East Asian (EAS) AF: 0.456 AC: 2339 AN: 5130

South Asian (SAS) AF: 0.533 AC: 2555 AN: 4798

European-Finnish (FIN) AF: 0.371 AC: 3920 AN: 10560

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.464 AC: 31489 AN: 67934

Other (OTH) AF: 0.385 AC: 812 AN: 2110

Alfa AF: 0.433 Hom.: 27298

Bravo AF: 0.364

Asia WGS AF: 0.471 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.71
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs1892318; hg19: chr20-59988069;