5-19560422-G-A

Position:

• chr5-19560422-G-A

Variant summary

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

The NM_004934.5(CDH18):​c.1253+11157C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0993 in 151,932 control chromosomes in the GnomAD database, including 1,040 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 0.099 (1040 hom., cov: 33)
• Consequence: CDH18 NM_004934.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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 (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH18	NM_004934.5	c.1253+11157C>T		intron_variant		ENST00000382275.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH18	ENST00000382275.6	c.1253+11157C>T		intron_variant		1	NM_004934.5	P1

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 15050 AN: 151814 Hom.: 1029 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0855

Gnomad ASJ AF: 0.0710

Gnomad EAS AF: 0.0966

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0594

Gnomad OTH AF: 0.0964

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

GnomAD4 genome AF: 0.0993 AC: 15094 AN: 151932 Hom.: 1040 Cov.: 33 AF XY: 0.0982 AC XY: 7292 AN XY: 74256

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0857

Gnomad4 ASJ AF: 0.0710

Gnomad4 EAS AF: 0.0962

Gnomad4 SAS AF: 0.0440

Gnomad4 FIN AF: 0.0473

Gnomad4 NFE AF: 0.0595

Gnomad4 OTH AF: 0.0964

Alfa AF: 0.0778 Hom.: 90

Bravo AF: 0.108

Asia WGS AF: 0.0850 AC: 296 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	1.1
DANN	Benign	0.26

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: rs394241; hg19: chr5-19560531;