5-19623034-C-T

Position:

• chr5-19623034-C-T

Variant summary

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

The NM_004934.5(CDH18):​c.644-10433G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,024 control chromosomes in the GnomAD database, including 32,327 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 0.65 (32327 hom., cov: 32)
• Consequence: CDH18 NM_004934.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH18	NM_004934.5	c.644-10433G>A		intron_variant		ENST00000382275.6	NP_004925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH18	ENST00000382275.6	c.644-10433G>A		intron_variant		1	NM_004934.5	ENSP00000371710	P1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98290 AN: 151906 Hom.: 32314 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.647 AC: 98336 AN: 152024 Hom.: 32327 Cov.: 32 AF XY: 0.646 AC XY: 47996 AN XY: 74300

Gnomad4 AFR AF: 0.514

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.669

Alfa AF: 0.686 Hom.: 13429

Bravo AF: 0.641

Asia WGS AF: 0.762 AC: 2652 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	0.075
DANN	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1374489; hg19: chr5-19623143;