rs6061845

Positions:

• chr20-61823748-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.577-20920G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,026 control chromosomes in the GnomAD database, including 30,011 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 0.62 (30011 hom., cov: 32)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH4	NM_001794.5	c.577-20920G>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.577-20920G>A		intron_variant		1	NM_001794.5	ENSP00000484928.1
CDH4	ENST00000543233.2	c.355-20920G>A		intron_variant		2		ENSP00000443301.1
CDH4	ENST00000611855.4	c.295-20920G>A		intron_variant		5		ENSP00000480844.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94843 AN: 151908 Hom.: 29975 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.624 AC: 94929 AN: 152026 Hom.: 30011 Cov.: 32 AF XY: 0.618 AC XY: 45949 AN XY: 74302

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.649

Gnomad4 OTH AF: 0.614

Alfa AF: 0.640 Hom.: 48167

Bravo AF: 0.621

Asia WGS AF: 0.452 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.77

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: rs6061845; hg19: chr20-60398804;