rs16985437

Positions:

• chr20-61683795-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001794.5(CDH4):​c.170-59768G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 152,322 control chromosomes in the GnomAD database, including 302 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 0.046 (302 hom., cov: 33)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH4	NM_001794.5	c.170-59768G>A		intron_variant		ENST00000614565.5	NP_001785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH4	ENST00000614565.5	c.170-59768G>A		intron_variant		1	NM_001794.5	ENSP00000484928	P1
CDH4	ENST00000543233.2	c.-53-59768G>A		intron_variant		2		ENSP00000443301
CDH4	ENST00000611855.4	c.50-59768G>A		intron_variant		5		ENSP00000480844

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6935 AN: 152204 Hom.: 296 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0488

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

GnomAD4 genome AF: 0.0457 AC: 6966 AN: 152322 Hom.: 302 Cov.: 33 AF XY: 0.0458 AC XY: 3408 AN XY: 74486

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0350

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0802

Gnomad4 FIN AF: 0.00292

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.0526

Alfa AF: 0.0311 Hom.: 23

Bravo AF: 0.0489

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs16985437; hg19: chr20-60258851;