rs944260

Positions:

• chr20-61668355-G-A
• chr20-61668355-G-T

Variant summary

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

The NM_001794.5(CDH4):​c.170-75208G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,206 control chromosomes in the GnomAD database, including 41,377 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 0.74 (41377 hom., cov: 34)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH4	NM_001794.5	c.170-75208G>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.170-75208G>A		intron_variant		1	NM_001794.5	ENSP00000484928.1
CDH4	ENST00000543233.2	c.-54+68366G>A		intron_variant		2		ENSP00000443301.1
CDH4	ENST00000611855.4	c.50-75208G>A		intron_variant		5		ENSP00000480844.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112033 AN: 152088 Hom.: 41338 Cov.: 34

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.737 AC: 112125 AN: 152206 Hom.: 41377 Cov.: 34 AF XY: 0.735 AC XY: 54721 AN XY: 74414

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.731

Alfa AF: 0.713 Hom.: 69224

Bravo AF: 0.735

Asia WGS AF: 0.661 AC: 2296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.41
DANN	Benign	0.31

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: rs944260; hg19: chr20-60243411;