chr20-61743735-C-T

Variant names:

• chr20-61743735-C-T
• rs776377387
• NM_001794.5:c.342C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001794.5(CDH4):​c.342C>T​(p.Asp114Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000509 in 1,610,832 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: CDH4 NM_001794.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.48
• 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

CDH4-AS1 (HGNC:40139):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-3.48 with no splicing effect.

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.342C>T	p.Asp114Asp	synonymous	Exon 3 of 16	NP_001785.2
	CDH4	NM_001252338.2		c.231C>T	p.Asp77Asp	synonymous	Exon 2 of 15	NP_001239267.1
	CDH4	NM_001252339.3		c.120C>T	p.Asp40Asp	synonymous	Exon 2 of 15	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.342C>T	p.Asp114Asp	synonymous	Exon 3 of 16	ENSP00000484928.1	P55283-1
	CDH4	ENST00000543233.2	TSL:2	c.120C>T	p.Asp40Asp	synonymous	Exon 2 of 15	ENSP00000443301.1	P55283-2
	CDH4	ENST00000611855.4	TSL:5	c.114+108C>T		intron	N/A	ENSP00000480844.1	A0A087WX99

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000416 AC: 10 AN: 240356 AF XY: 0.0000383

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000885

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000554

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000370

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000494 AC: 72 AN: 1458478 Hom.: 0 Cov.: 32 AF XY: 0.0000469 AC XY: 34 AN XY: 725122

African (AFR) AF: 0.000149 AC: 5 AN: 33458

American (AMR) AF: 0.0000676 AC: 3 AN: 44378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39608

South Asian (SAS) AF: 0.0000703 AC: 6 AN: 85376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52764

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5764

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1110842

Other (OTH) AF: 0.0000830 AC: 5 AN: 60238

GnomAD4 genome AF: 0.0000656 AC: 10 AN: 152354 Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5 AN XY: 74496

African (AFR) AF: 0.000144 AC: 6 AN: 41590

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000986 Hom.: 0

Bravo AF: 0.0000680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.7
DANN	Benign	0.90
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism

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: rs776377387; hg19: chr20-60318791; COSMIC: COSV64670683;