rs3784847

Positions:

• chr16-61943545-A-G

Variant summary

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

The NM_001796.5(CDH8):​c.253-42072T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 152,280 control chromosomes in the GnomAD database, including 955 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 0.098 (955 hom., cov: 33)
• Consequence: CDH8 NM_001796.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

Genes affected

CDH8 (HGNC:1767): (cadherin 8) This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein's homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is expressed in brain and is putatively involved in synaptic adhesion, axon outgrowth and guidance. [provided by RefSeq, Jul 2008]

CDH8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH8	NM_001796.5	c.253-42072T>C		intron_variant		ENST00000577390.6	NP_001787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH8	ENST00000577390.6	c.253-42072T>C		intron_variant		1	NM_001796.5	ENSP00000462701.1

Frequencies

GnomAD3 genomes AF: 0.0978 AC: 14875 AN: 152162 Hom.: 948 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0917

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

GnomAD4 genome AF: 0.0978 AC: 14890 AN: 152280 Hom.: 955 Cov.: 33 AF XY: 0.100 AC XY: 7466 AN XY: 74460

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.0673

Gnomad4 OTH AF: 0.0893

Alfa AF: 0.0760 Hom.: 593

Bravo AF: 0.104

Asia WGS AF: 0.210 AC: 730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.5
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: rs3784847; hg19: chr16-61977449;