20-61758177-C-T

Variant names:

• chr20-61758177-C-T
• rs6061348
• NM_001794.5:c.396+14388C>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.396+14388C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,024 control chromosomes in the GnomAD database, including 2,889 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 0.18 (2889 hom., cov: 33)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH4	NM_001794.5	c.396+14388C>T		intron_variant	Intron 3 of 15	ENST00000614565.5	NP_001785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH4	ENST00000614565.5	c.396+14388C>T		intron_variant	Intron 3 of 15	1	NM_001794.5	ENSP00000484928.1
CDH4	ENST00000543233.2	c.174+14388C>T		intron_variant	Intron 2 of 14	2		ENSP00000443301.1
CDH4	ENST00000611855.4	c.114+14550C>T		intron_variant	Intron 2 of 14	5		ENSP00000480844.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28068 AN: 151906 Hom.: 2877 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.185 AC: 28118 AN: 152024 Hom.: 2889 Cov.: 33 AF XY: 0.184 AC XY: 13644 AN XY: 74288

African (AFR) AF: 0.262 AC: 10864 AN: 41458

American (AMR) AF: 0.165 AC: 2515 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3472

East Asian (EAS) AF: 0.0407 AC: 210 AN: 5162

South Asian (SAS) AF: 0.0737 AC: 355 AN: 4818

European-Finnish (FIN) AF: 0.194 AC: 2049 AN: 10566

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10910 AN: 67950

Other (OTH) AF: 0.174 AC: 366 AN: 2106

Alfa AF: 0.161 Hom.: 3558

Bravo AF: 0.188

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.48
PhyloP100		-1.1
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: rs6061348; hg19: chr20-60333233;