20-61637438-C-T

Variant names:

• chr20-61637438-C-T
• rs2024714
• NM_001794.5:c.170-106125C>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.170-106125C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,012 control chromosomes in the GnomAD database, including 28,117 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 0.61 (28117 hom., cov: 32)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 13 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH4	NM_001794.5	c.170-106125C>T		intron_variant	Intron 2 of 15	ENST00000614565.5	NP_001785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH4	ENST00000614565.5	c.170-106125C>T		intron_variant	Intron 2 of 15	1	NM_001794.5	ENSP00000484928.1
CDH4	ENST00000543233.2	c.-54+37449C>T		intron_variant	Intron 1 of 14	2		ENSP00000443301.1
CDH4	ENST00000611855.4	c.49+66695C>T		intron_variant	Intron 1 of 14	5		ENSP00000480844.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91920 AN: 151892 Hom.: 28089 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.605 AC: 91995 AN: 152012 Hom.: 28117 Cov.: 32 AF XY: 0.607 AC XY: 45119 AN XY: 74304

African (AFR) AF: 0.672 AC: 27828 AN: 41430

American (AMR) AF: 0.568 AC: 8676 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2295 AN: 3466

East Asian (EAS) AF: 0.707 AC: 3648 AN: 5158

South Asian (SAS) AF: 0.696 AC: 3355 AN: 4822

European-Finnish (FIN) AF: 0.600 AC: 6344 AN: 10574

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

European-Non Finnish (NFE) AF: 0.559 AC: 37958 AN: 67958

Other (OTH) AF: 0.599 AC: 1266 AN: 2112

Alfa AF: 0.580 Hom.: 35745

Bravo AF: 0.602

Asia WGS AF: 0.714 AC: 2482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.87
PhyloP100		-2.1
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: rs2024714; hg19: chr20-60212494;