rs4386736

Variant names:

• chr5-20432230-C-T
• rs4386736
• NM_001291956.3:c.-580+143232G>A

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+143232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,990 control chromosomes in the GnomAD database, including 3,881 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 0.22 (3881 hom., cov: 32)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH18	NM_001291956.3		c.-580+143232G>A		intron	N/A	NP_001278885.1	Q13634-1
	CDH18	NM_001349556.2		c.-434+143232G>A		intron	N/A	NP_001336485.1	Q13634-1
	CDH18	NM_001349558.2		c.-727-93991G>A		intron	N/A	NP_001336487.1	Q13634-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH18	ENST00000507958.5	TSL:2	c.-580+143232G>A		intron	N/A	ENSP00000425093.1	Q13634-1
	CDH18	ENST00000507632.2	TSL:4	n.402+143232G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33513 AN: 151870 Hom.: 3880 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.221 AC: 33530 AN: 151990 Hom.: 3881 Cov.: 32 AF XY: 0.219 AC XY: 16282 AN XY: 74276

African (AFR) AF: 0.198 AC: 8211 AN: 41464

American (AMR) AF: 0.138 AC: 2115 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3464

East Asian (EAS) AF: 0.298 AC: 1529 AN: 5138

South Asian (SAS) AF: 0.233 AC: 1122 AN: 4820

European-Finnish (FIN) AF: 0.264 AC: 2786 AN: 10560

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16497 AN: 67950

Other (OTH) AF: 0.190 AC: 401 AN: 2110

Alfa AF: 0.229 Hom.: 744

Bravo AF: 0.211

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.73
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4386736;

hg19: chr5-20432339;