chr5-20439782-C-T

Position:

• chr5-20439782-C-T

Variant summary

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

The NM_001291956.3(CDH18):​c.-580+135680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,402 control chromosomes in the GnomAD database, including 3,178 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 0.18 (3178 hom., cov: 32)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH18	NM_001291956.3	c.-580+135680G>A		intron_variant
CDH18	NM_001349556.2	c.-434+135680G>A		intron_variant
CDH18	NM_001349558.2	c.-727-101543G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH18	ENST00000507958.5	c.-580+135680G>A		intron_variant		2		P1
CDH18	ENST00000507632.2	n.402+135680G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27855 AN: 151284 Hom.: 3177 Cov.: 32

Gnomad AFR AF: 0.0780

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.184 AC: 27848 AN: 151402 Hom.: 3178 Cov.: 32 AF XY: 0.183 AC XY: 13523 AN XY: 73968

Gnomad4 AFR AF: 0.0778

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.170

Alfa AF: 0.213 Hom.: 4082

Bravo AF: 0.170

Asia WGS AF: 0.211 AC: 730 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13357704; hg19: chr5-20439891;