rs6061612

Variant names:

• chr20-61532516-G-A
• rs6061612
• NM_001794.5:c.170-211047G>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.170-211047G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,074 control chromosomes in the GnomAD database, including 17,916 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 0.42 (17916 hom., cov: 33)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.87
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH4	NM_001794.5	c.170-211047G>A		intron_variant	Intron 2 of 15	ENST00000614565.5	NP_001785.2
CDH4	NM_001252338.2	c.58+33024G>A		intron_variant	Intron 1 of 14		NP_001239267.1
CDH4	XM_047439812.1	c.-53-211047G>A		intron_variant	Intron 2 of 15		XP_047295768.1
CDH4	XM_047439813.1	c.-53-211047G>A		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.170-211047G>A		intron_variant	Intron 2 of 15	1	NM_001794.5	ENSP00000484928.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63631 AN: 151954 Hom.: 17849 Cov.: 33

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.419 AC: 63762 AN: 152074 Hom.: 17916 Cov.: 33 AF XY: 0.414 AC XY: 30766 AN XY: 74326

African (AFR) AF: 0.804 AC: 33367 AN: 41494

American (AMR) AF: 0.349 AC: 5331 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1105 AN: 3472

East Asian (EAS) AF: 0.451 AC: 2330 AN: 5164

South Asian (SAS) AF: 0.207 AC: 997 AN: 4818

European-Finnish (FIN) AF: 0.252 AC: 2662 AN: 10568

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16852 AN: 67964

Other (OTH) AF: 0.406 AC: 855 AN: 2106

Alfa AF: 0.365 Hom.: 11993

Bravo AF: 0.448

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.030
DANN	Benign	0.62
PhyloP100		-3.9
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: rs6061612; hg19: chr20-60107572;