rs13355121

Variant names:

• chr5-20437452-G-C
• rs13355121
• NM_001291956.3:c.-580+138010C>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+138010C>G 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 151,080 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: -0.0110
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH18	NM_001291956.3	c.-580+138010C>G		intron_variant	Intron 1 of 14		NP_001278885.1
CDH18	NM_001349556.2	c.-434+138010C>G		intron_variant	Intron 1 of 13		NP_001336485.1
CDH18	NM_001349558.2	c.-727-99213C>G		intron_variant	Intron 1 of 15		NP_001336487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH18	ENST00000507958.5	c.-580+138010C>G		intron_variant	Intron 1 of 14	2		ENSP00000425093.1
CDH18	ENST00000507632.2	n.402+138010C>G		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32280 AN: 150962 Hom.: 3798 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.242

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: 32295 AN: 151080 Hom.: 3799 Cov.: 31 AF XY: 0.212 AC XY: 15663 AN XY: 73770

African (AFR) AF: 0.175 AC: 7179 AN: 41100

American (AMR) AF: 0.135 AC: 2045 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3460

East Asian (EAS) AF: 0.297 AC: 1532 AN: 5154

South Asian (SAS) AF: 0.234 AC: 1127 AN: 4820

European-Finnish (FIN) AF: 0.264 AC: 2777 AN: 10536

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.242 AC: 16372 AN: 67540

Other (OTH) AF: 0.187 AC: 393 AN: 2100

Alfa AF: 0.237 Hom.: 568

Bravo AF: 0.203

Asia WGS AF: 0.258 AC: 889 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.68
PhyloP100		-0.011
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: rs13355121; hg19: chr5-20437561;