rs4925295

Variant names:

• chr20-61806743-G-A
• rs4925295
• NM_001794.5:c.576+33561G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-61806743-G-A
• chr20-61806743-G-C
• chr20-61806743-G-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.576+33561G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,120 control chromosomes in the GnomAD database, including 58,896 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 0.88 (58896 hom., cov: 32)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH4	NM_001794.5	MANE Select	c.576+33561G>A		intron	N/A	NP_001785.2
	CDH4	NM_001252338.2		c.465+33561G>A		intron	N/A	NP_001239267.1
	CDH4	NM_001252339.3		c.354+33561G>A		intron	N/A	NP_001239268.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH4	ENST00000614565.5	TSL:1 MANE Select	c.576+33561G>A		intron	N/A	ENSP00000484928.1
	CDH4	ENST00000543233.2	TSL:2	c.354+33561G>A		intron	N/A	ENSP00000443301.1
	CDH4	ENST00000611855.4	TSL:5	c.294+33561G>A		intron	N/A	ENSP00000480844.1

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133597 AN: 152002 Hom.: 58828 Cov.: 32

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.834

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.860

Gnomad OTH AF: 0.836

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

GnomAD4 genome AF: 0.879 AC: 133726 AN: 152120 Hom.: 58896 Cov.: 32 AF XY: 0.881 AC XY: 65539 AN XY: 74368

African (AFR) AF: 0.916 AC: 37983 AN: 41486

American (AMR) AF: 0.834 AC: 12752 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2848 AN: 3472

East Asian (EAS) AF: 0.925 AC: 4760 AN: 5146

South Asian (SAS) AF: 0.907 AC: 4373 AN: 4820

European-Finnish (FIN) AF: 0.918 AC: 9722 AN: 10592

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.860 AC: 58466 AN: 67996

Other (OTH) AF: 0.839 AC: 1771 AN: 2110

Alfa AF: 0.859 Hom.: 107506

Bravo AF: 0.870

Asia WGS AF: 0.904 AC: 3144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		-0.27
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: rs4925295; hg19: chr20-60381799;