rs13040920

Positions:

• chr20-61817605-T-C

Variant summary

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

The NM_001794.5(CDH4):​c.577-27063T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,866 control chromosomes in the GnomAD database, including 20,894 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 0.51 (20894 hom., cov: 32)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH4	NM_001794.5	c.577-27063T>C		intron_variant		ENST00000614565.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH4	ENST00000614565.5	c.577-27063T>C		intron_variant		1	NM_001794.5	P1
CDH4	ENST00000543233.2	c.355-27063T>C		intron_variant		2
CDH4	ENST00000611855.4	c.295-27063T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77552 AN: 151746 Hom.: 20869 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.511 AC: 77619 AN: 151866 Hom.: 20894 Cov.: 32 AF XY: 0.509 AC XY: 37799 AN XY: 74198

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.514

Alfa AF: 0.575 Hom.: 11575

Bravo AF: 0.499

Asia WGS AF: 0.428 AC: 1489 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	1.1
DANN	Benign	0.29

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: rs13040920; hg19: chr20-60392661;