rs6121489

Positions:

• chr20-61911442-C-T

Variant summary

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

The ENST00000614565.5(CDH4):​c.1374+835C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0513 in 152,256 control chromosomes in the GnomAD database, including 762 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 0.051 (762 hom., cov: 34)
• Consequence: CDH4 ENST00000614565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH4	NM_001794.5	c.1374+835C>T		intron_variant		ENST00000614565.5	NP_001785.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH4	ENST00000614565.5	c.1374+835C>T		intron_variant		1	NM_001794.5	ENSP00000484928	P1
CDH4	ENST00000543233.2	c.1152+835C>T		intron_variant		2		ENSP00000443301
CDH4	ENST00000611855.4	c.1092+835C>T		intron_variant		5		ENSP00000480844

Frequencies

GnomAD3 genomes AF: 0.0513 AC: 7800 AN: 152138 Hom.: 753 Cov.: 34

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0855

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00513

Gnomad OTH AF: 0.0478

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

GnomAD4 genome AF: 0.0513 AC: 7818 AN: 152256 Hom.: 762 Cov.: 34 AF XY: 0.0585 AC XY: 4352 AN XY: 74430

Gnomad4 AFR AF: 0.0546

Gnomad4 AMR AF: 0.0864

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0695

Gnomad4 NFE AF: 0.00513

Gnomad4 OTH AF: 0.0488

Alfa AF: 0.0241 Hom.: 29

Bravo AF: 0.0545

Asia WGS AF: 0.247 AC: 856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.3
DANN	Benign	0.51

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: rs6121489; hg19: chr20-60486498;