rs6061612

Positions:

• chr20-61532516-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.170-211047G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,074 control chromosomes in the GnomAD database, including 17,916 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 0.42 (17916 hom., cov: 33)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.87

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH4	NM_001794.5	c.170-211047G>A		intron_variant		ENST00000614565.5
CDH4	NM_001252338.2	c.58+33024G>A		intron_variant
CDH4	XM_047439812.1	c.-53-211047G>A		intron_variant
CDH4	XM_047439813.1	c.-53-211047G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH4	ENST00000614565.5	c.170-211047G>A		intron_variant		1	NM_001794.5	P1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63631 AN: 151954 Hom.: 17849 Cov.: 33

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.419 AC: 63762 AN: 152074 Hom.: 17916 Cov.: 33 AF XY: 0.414 AC XY: 30766 AN XY: 74326

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.406

Alfa AF: 0.288 Hom.: 4424

Bravo AF: 0.448

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.030
DANN	Benign	0.62

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: rs6061612; hg19: chr20-60107572;