rs883067

Positions:

• chr5-19713524-T-C

Variant summary

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

The NM_004934.5(CDH18):​c.643+7823A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,070 control chromosomes in the GnomAD database, including 3,841 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 0.21 (3841 hom., cov: 32)
• Consequence: CDH18 NM_004934.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

Genes affected

CDH18 (HGNC:1757): (cadherin 18) This gene encodes a type II classical cadherin from the cadherin superfamily of 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. 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 specifically in the central nervous system and is putatively involved in synaptic adhesion, axon outgrowth and guidance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH18	NM_004934.5	c.643+7823A>G		intron_variant		ENST00000382275.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH18	ENST00000382275.6	c.643+7823A>G		intron_variant		1	NM_004934.5	P1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31882 AN: 151950 Hom.: 3842 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.210 AC: 31878 AN: 152070 Hom.: 3841 Cov.: 32 AF XY: 0.212 AC XY: 15792 AN XY: 74318

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.202

Alfa AF: 0.242 Hom.: 2144

Bravo AF: 0.200

Asia WGS AF: 0.0830 AC: 289 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.50

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: rs883067; hg19: chr5-19713633;