5-20455487-G-C

Position:

• chr5-20455487-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291956.3(CDH18):​c.-580+119975C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 151,776 control chromosomes in the GnomAD database, including 38,538 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 0.70 (38538 hom., cov: 30)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH18	NM_001291956.3	c.-580+119975C>G		intron_variant			NP_001278885.1
CDH18	NM_001349556.2	c.-434+119975C>G		intron_variant			NP_001336485.1
CDH18	NM_001349558.2	c.-727-117248C>G		intron_variant			NP_001336487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH18	ENST00000507958.5	c.-580+119975C>G		intron_variant		2		ENSP00000425093	P1
CDH18	ENST00000507632.2	n.402+119975C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106809 AN: 151658 Hom.: 38508 Cov.: 30

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.704 AC: 106886 AN: 151776 Hom.: 38538 Cov.: 30 AF XY: 0.709 AC XY: 52557 AN XY: 74154

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.834

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.747

Alfa AF: 0.625 Hom.: 1817

Bravo AF: 0.704

Asia WGS AF: 0.719 AC: 2501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10805723; hg19: chr5-20455596;