5-20464618-T-C

Variant names:

• chr5-20464618-T-C
• rs10062864
• NM_001291956.3:c.-580+110844A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291956.3(CDH18):​c.-580+110844A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,030 control chromosomes in the GnomAD database, including 47,375 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 0.79 (47375 hom., cov: 32)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 2 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291956.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH18	NM_001291956.3		c.-580+110844A>G		intron	N/A	NP_001278885.1
	CDH18	NM_001349556.2		c.-434+110844A>G		intron	N/A	NP_001336485.1
	CDH18	NM_001349558.2		c.-728+110844A>G		intron	N/A	NP_001336487.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH18	ENST00000507958.5	TSL:2	c.-580+110844A>G		intron	N/A	ENSP00000425093.1
	CDH18	ENST00000507632.2	TSL:4	n.402+110844A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119605 AN: 151912 Hom.: 47321 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.787 AC: 119715 AN: 152030 Hom.: 47375 Cov.: 32 AF XY: 0.790 AC XY: 58714 AN XY: 74310

African (AFR) AF: 0.824 AC: 34167 AN: 41488

American (AMR) AF: 0.862 AC: 13161 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2928 AN: 3466

East Asian (EAS) AF: 0.706 AC: 3632 AN: 5144

South Asian (SAS) AF: 0.816 AC: 3934 AN: 4820

European-Finnish (FIN) AF: 0.736 AC: 7793 AN: 10588

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51546 AN: 67948

Other (OTH) AF: 0.806 AC: 1703 AN: 2112

Alfa AF: 0.776 Hom.: 7998

Bravo AF: 0.796

Asia WGS AF: 0.780 AC: 2714 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.097
DANN	Benign	0.42
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10062864; hg19: chr5-20464727;