rs4468878

Variant names:

• chr20-61353181-T-C
• rs4468878
• NM_001794.5:c.169+98244T>C

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+98244T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 152,012 control chromosomes in the GnomAD database, including 20,403 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 0.51 (20403 hom., cov: 32)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 16 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH4	NM_001794.5	c.169+98244T>C		intron_variant	Intron 2 of 15	ENST00000614565.5	NP_001785.2
CDH4	XM_047439812.1	c.-54+98244T>C		intron_variant	Intron 2 of 15		XP_047295768.1
CDH4	XM_047439813.1	c.-54+98244T>C		intron_variant	Intron 2 of 15		XP_047295769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH4	ENST00000614565.5	c.169+98244T>C		intron_variant	Intron 2 of 15	1	NM_001794.5	ENSP00000484928.1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77655 AN: 151894 Hom.: 20381 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.511 AC: 77717 AN: 152012 Hom.: 20403 Cov.: 32 AF XY: 0.510 AC XY: 37878 AN XY: 74282

African (AFR) AF: 0.399 AC: 16535 AN: 41456

American (AMR) AF: 0.503 AC: 7692 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2528 AN: 3472

East Asian (EAS) AF: 0.474 AC: 2431 AN: 5128

South Asian (SAS) AF: 0.570 AC: 2743 AN: 4816

European-Finnish (FIN) AF: 0.478 AC: 5055 AN: 10580

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38995 AN: 67946

Other (OTH) AF: 0.531 AC: 1123 AN: 2116

Alfa AF: 0.556 Hom.: 68374

Bravo AF: 0.504

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.015
DANN	Benign	0.49
PhyloP100		-2.0
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: rs4468878; hg19: chr20-59928237;