5-20438559-C-T

Variant summary

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

The NM_001291956.3(CDH18):c.-580+136903G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 150,954 control chromosomes in the GnomAD database, including 3,799 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 (3799 hom., cov: 31)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH18	NM_001291956.3	c.-580+136903G>A		intron_variant
CDH18	NM_001349556.2	c.-434+136903G>A		intron_variant
CDH18	NM_001349558.2	c.-727-100320G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH18	ENST00000507958.5	c.-580+136903G>A		intron_variant		2		P1
CDH18	ENST00000507632.2	n.402+136903G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32282 AN: 150836 Hom.: 3798 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.214 AC: 32296 AN: 150954 Hom.: 3799 Cov.: 31 AF XY: 0.212 AC XY: 15666 AN XY: 73746

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.187

Alfa AF: 0.163 Hom.: 463

Bravo AF: 0.203

Asia WGS AF: 0.259 AC: 900 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.1
Dann	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16887308; hg19: chr5-20438668;