rs6089621

Positions:

• chr20-61436301-T-G

Variant summary

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

The NM_001794.5(CDH4):​c.169+181364T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0735 in 152,242 control chromosomes in the GnomAD database, including 677 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 0.074 (677 hom., cov: 33)
• Consequence: CDH4 NM_001794.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH4	NM_001794.5	c.169+181364T>G		intron_variant		ENST00000614565.5
LOC105372703	XR_007067696.1	n.2269+740A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH4	ENST00000614565.5	c.169+181364T>G		intron_variant		1	NM_001794.5	P1
	ENST00000662116.1	n.590+740A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 11183 AN: 152124 Hom.: 675 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.0527

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0584

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

GnomAD4 genome AF: 0.0735 AC: 11194 AN: 152242 Hom.: 677 Cov.: 33 AF XY: 0.0712 AC XY: 5304 AN XY: 74446

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0311

Gnomad4 FIN AF: 0.0527

Gnomad4 NFE AF: 0.0442

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0624 Hom.: 65

Bravo AF: 0.0770

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.72

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: rs6089621; hg19: chr20-60011357;