rs445021

Positions:

• chr5-19551756-G-C
• chr5-19551756-G-T

Variant summary

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

The NM_004934.5(CDH18):​c.1254-7751C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 152,090 control chromosomes in the GnomAD database, including 55,864 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 0.85 (55864 hom., cov: 32)
• Consequence: CDH18 NM_004934.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH18	NM_004934.5	c.1254-7751C>G		intron_variant		ENST00000382275.6	NP_004925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH18	ENST00000382275.6	c.1254-7751C>G		intron_variant		1	NM_004934.5	ENSP00000371710	P1

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129951 AN: 151970 Hom.: 55839 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.855 AC: 130030 AN: 152090 Hom.: 55864 Cov.: 32 AF XY: 0.853 AC XY: 63427 AN XY: 74344

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.906

Gnomad4 OTH AF: 0.856

Alfa AF: 0.873 Hom.: 6803

Bravo AF: 0.848

Asia WGS AF: 0.811 AC: 2818 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.46

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: rs445021; hg19: chr5-19551865;