chr5-20556333-G-T

Variant names:

• chr5-20556333-G-T
• rs10520868
• NM_001291956.3:c.-580+19129C>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+19129C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 152,204 control chromosomes in the GnomAD database, including 95 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 0.027 (95 hom., cov: 32)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188
• Publications: 0 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH18	NM_001291956.3	c.-580+19129C>A		intron_variant	Intron 1 of 14		NP_001278885.1
CDH18	NM_001349556.2	c.-434+19129C>A		intron_variant	Intron 1 of 13		NP_001336485.1
CDH18	NM_001349558.2	c.-728+19129C>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+19129C>A		intron_variant	Intron 1 of 14	2		ENSP00000425093.1
CDH18	ENST00000507632.2	n.402+19129C>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4105 AN: 152086 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0225

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

GnomAD4 genome AF: 0.0270 AC: 4108 AN: 152204 Hom.: 95 Cov.: 32 AF XY: 0.0266 AC XY: 1980 AN XY: 74408

African (AFR) AF: 0.0636 AC: 2642 AN: 41512

American (AMR) AF: 0.0150 AC: 229 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.0161 AC: 78 AN: 4832

European-Finnish (FIN) AF: 0.0184 AC: 195 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0131 AC: 889 AN: 68018

Other (OTH) AF: 0.0223 AC: 47 AN: 2112

Alfa AF: 0.0331 Hom.: 11

Bravo AF: 0.0281

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.23
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10520868; hg19: chr5-20556442;