chr5-20438559-C-T

Variant names:

• chr5-20438559-C-T
• rs16887308
• NM_001291956.3:c.-580+136903G>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+136903G>A 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 150,954 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: -0.816
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH18	NM_001291956.3	c.-580+136903G>A		intron_variant	Intron 1 of 14		NP_001278885.1
CDH18	NM_001349556.2	c.-434+136903G>A		intron_variant	Intron 1 of 13		NP_001336485.1
CDH18	NM_001349558.2	c.-727-100320G>A		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+136903G>A		intron_variant	Intron 1 of 14	2		ENSP00000425093.1
CDH18	ENST00000507632.2	n.402+136903G>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32282 AN: 150836 Hom.: 3798 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.243

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: 32296 AN: 150954 Hom.: 3799 Cov.: 31 AF XY: 0.212 AC XY: 15666 AN XY: 73746

African (AFR) AF: 0.175 AC: 7157 AN: 40994

American (AMR) AF: 0.135 AC: 2056 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3458

East Asian (EAS) AF: 0.297 AC: 1527 AN: 5146

South Asian (SAS) AF: 0.233 AC: 1115 AN: 4792

European-Finnish (FIN) AF: 0.265 AC: 2786 AN: 10522

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.243 AC: 16396 AN: 67556

Other (OTH) AF: 0.187 AC: 394 AN: 2110

Alfa AF: 0.163 Hom.: 478

Bravo AF: 0.203

Asia WGS AF: 0.259 AC: 900 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.82
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: rs16887308; hg19: chr5-20438668;