rs883067

Variant names:

• chr5-19713524-T-C
• rs883067
• NM_004934.5:c.643+7823A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDH18	NM_004934.5	c.643+7823A>G		intron_variant	Intron 5 of 12	ENST00000382275.6	NP_004925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH18	ENST00000382275.6	c.643+7823A>G		intron_variant	Intron 5 of 12	1	NM_004934.5	ENSP00000371710.1

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

African (AFR) AF: 0.114 AC: 4733 AN: 41542

American (AMR) AF: 0.240 AC: 3657 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 810 AN: 3468

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5182

South Asian (SAS) AF: 0.197 AC: 949 AN: 4822

European-Finnish (FIN) AF: 0.343 AC: 3619 AN: 10564

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17423 AN: 67934

Other (OTH) AF: 0.202 AC: 426 AN: 2108

Alfa AF: 0.241 Hom.: 2387

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
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs883067; hg19: chr5-19713633;