rs1970546

Variant names:

• chr20-61278882-A-G
• rs1970546
• NM_001794.5:c.169+23945A>G

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+23945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,164 control chromosomes in the GnomAD database, including 39,516 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 0.72 (39516 hom., cov: 34)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 17 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH4	NM_001794.5	c.169+23945A>G		intron_variant	Intron 2 of 15	ENST00000614565.5	NP_001785.2
CDH4	XM_047439812.1	c.-54+23945A>G		intron_variant	Intron 2 of 15		XP_047295768.1
CDH4	XM_047439813.1	c.-54+23945A>G		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+23945A>G		intron_variant	Intron 2 of 15	1	NM_001794.5	ENSP00000484928.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109548 AN: 152046 Hom.: 39489 Cov.: 34

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.720 AC: 109627 AN: 152164 Hom.: 39516 Cov.: 34 AF XY: 0.720 AC XY: 53573 AN XY: 74380

African (AFR) AF: 0.699 AC: 29031 AN: 41510

American (AMR) AF: 0.769 AC: 11759 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2705 AN: 3470

East Asian (EAS) AF: 0.668 AC: 3444 AN: 5156

South Asian (SAS) AF: 0.762 AC: 3673 AN: 4822

European-Finnish (FIN) AF: 0.692 AC: 7336 AN: 10598

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49253 AN: 67996

Other (OTH) AF: 0.723 AC: 1526 AN: 2110

Alfa AF: 0.726 Hom.: 96270

Bravo AF: 0.722

Asia WGS AF: 0.726 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.38
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: rs1970546; hg19: chr20-59853938;