chr20-61346059-C-T

Variant names:

• chr20-61346059-C-T
• rs13045809
• NM_001794.5:c.169+91122C>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+91122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,200 control chromosomes in the GnomAD database, including 1,714 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 0.13 (1714 hom., cov: 33)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH4	NM_001794.5	c.169+91122C>T		intron_variant	Intron 2 of 15	ENST00000614565.5	NP_001785.2
CDH4	XM_047439812.1	c.-54+91122C>T		intron_variant	Intron 2 of 15		XP_047295768.1
CDH4	XM_047439813.1	c.-54+91122C>T		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+91122C>T		intron_variant	Intron 2 of 15	1	NM_001794.5	ENSP00000484928.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19937 AN: 152082 Hom.: 1715 Cov.: 33

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.179

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.131 AC: 19938 AN: 152200 Hom.: 1714 Cov.: 33 AF XY: 0.136 AC XY: 10145 AN XY: 74400

African (AFR) AF: 0.0328 AC: 1361 AN: 41546

American (AMR) AF: 0.207 AC: 3159 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3472

East Asian (EAS) AF: 0.317 AC: 1637 AN: 5168

South Asian (SAS) AF: 0.184 AC: 888 AN: 4822

European-Finnish (FIN) AF: 0.190 AC: 2014 AN: 10600

Middle Eastern (MID) AF: 0.169 AC: 49 AN: 290

European-Non Finnish (NFE) AF: 0.146 AC: 9922 AN: 67992

Other (OTH) AF: 0.152 AC: 320 AN: 2112

Alfa AF: 0.144 Hom.: 5462

Bravo AF: 0.128

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.34
PhyloP100		-0.62
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: rs13045809; hg19: chr20-59921115;