20-61668355-G-A

Variant names:

• chr20-61668355-G-A
• rs944260
• NM_001794.5:c.170-75208G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001794.5(CDH4):​c.170-75208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,206 control chromosomes in the GnomAD database, including 41,377 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 0.74 (41377 hom., cov: 34)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH4	NM_001794.5	MANE Select	c.170-75208G>A		intron	N/A	NP_001785.2
	CDH4	NM_001252338.2		c.59-75208G>A		intron	N/A	NP_001239267.1
	CDH4	NM_001252339.3		c.-54+68366G>A		intron	N/A	NP_001239268.1	P55283-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH4	ENST00000614565.5	TSL:1 MANE Select	c.170-75208G>A		intron	N/A	ENSP00000484928.1	P55283-1
	CDH4	ENST00000543233.2	TSL:2	c.-54+68366G>A		intron	N/A	ENSP00000443301.1	P55283-2
	CDH4	ENST00000611855.4	TSL:5	c.50-75208G>A		intron	N/A	ENSP00000480844.1	A0A087WX99

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112033 AN: 152088 Hom.: 41338 Cov.: 34

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.737 AC: 112125 AN: 152206 Hom.: 41377 Cov.: 34 AF XY: 0.735 AC XY: 54721 AN XY: 74414

African (AFR) AF: 0.779 AC: 32341 AN: 41526

American (AMR) AF: 0.740 AC: 11317 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2330 AN: 3472

East Asian (EAS) AF: 0.572 AC: 2955 AN: 5168

South Asian (SAS) AF: 0.723 AC: 3487 AN: 4826

European-Finnish (FIN) AF: 0.749 AC: 7944 AN: 10606

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49453 AN: 67996

Other (OTH) AF: 0.731 AC: 1540 AN: 2108

Alfa AF: 0.721 Hom.: 159071

Bravo AF: 0.735

Asia WGS AF: 0.661 AC: 2296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.41
DANN	Benign	0.31
PhyloP100		-1.0
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: rs944260; hg19: chr20-60243411;