rs1911864

chr5-19966188-A-G

Variant summary

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

The NM_004934.5(CDH18):c.-257+14872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,952 control chromosomes in the GnomAD database, including 26,952 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 0.59 (26952 hom., cov: 32)
• Consequence: CDH18 NM_004934.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH18	NM_004934.5	c.-257+14872T>C		intron_variant		ENST00000382275.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH18	ENST00000382275.6	c.-257+14872T>C		intron_variant		1	NM_004934.5	P1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89954 AN: 151832 Hom.: 26938 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.592 AC: 90022 AN: 151952 Hom.: 26952 Cov.: 32 AF XY: 0.587 AC XY: 43573 AN XY: 74236

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.614

Alfa AF: 0.571 Hom.: 4559

Bravo AF: 0.594

Asia WGS AF: 0.643 AC: 2233 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.0
Dann	Benign	0.64

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: rs1911864; hg19: chr5-19966297;