rs116896199

chr20-61531817-A-G

Variant summary

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

The NM_001794.5(CDH4):c.170-211746A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 152,326 control chromosomes in the GnomAD database, including 99 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 0.015 (99 hom., cov: 33)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.41

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=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH4	NM_001794.5	c.170-211746A>G		intron_variant		ENST00000614565.5
CDH4	NM_001252338.2	c.58+32325A>G		intron_variant
CDH4	XM_047439812.1	c.-53-211746A>G		intron_variant
CDH4	XM_047439813.1	c.-53-211746A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH4	ENST00000614565.5	c.170-211746A>G		intron_variant		1	NM_001794.5	P1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2227 AN: 152208 Hom.: 99 Cov.: 33

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0805

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00195

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0146 AC: 2228 AN: 152326 Hom.: 99 Cov.: 33 AF XY: 0.0174 AC XY: 1293 AN XY: 74494

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.0781

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.0805

Gnomad4 SAS AF: 0.00496

Gnomad4 FIN AF: 0.0344

Gnomad4 NFE AF: 0.00196

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0105 Hom.: 4

Bravo AF: 0.0197

Asia WGS AF: 0.0310 AC: 109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	8.2
Dann	Benign	0.46

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: rs116896199; hg19: chr20-60106873;