rs394241

Variant names:

• chr5-19560422-G-A
• rs394241
• NM_004934.5:c.1253+11157C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004934.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH18	NM_004934.5	MANE Select	c.1253+11157C>T		intron	N/A	NP_004925.1
	CDH18	NM_001291956.3		c.1253+11157C>T		intron	N/A	NP_001278885.1
	CDH18	NM_001349556.2		c.1253+11157C>T		intron	N/A	NP_001336485.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH18	ENST00000382275.6	TSL:1 MANE Select	c.1253+11157C>T		intron	N/A	ENSP00000371710.1
	CDH18	ENST00000274170.8	TSL:1	c.1253+11157C>T		intron	N/A	ENSP00000274170.3
	CDH18	ENST00000506372.5	TSL:1	c.1253+11157C>T		intron	N/A	ENSP00000424931.1

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

African (AFR) AF: 0.195 AC: 8079 AN: 41472

American (AMR) AF: 0.0857 AC: 1307 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0710 AC: 246 AN: 3464

East Asian (EAS) AF: 0.0962 AC: 496 AN: 5154

South Asian (SAS) AF: 0.0440 AC: 212 AN: 4822

European-Finnish (FIN) AF: 0.0473 AC: 502 AN: 10602

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0595 AC: 4035 AN: 67862

Other (OTH) AF: 0.0964 AC: 203 AN: 2106

Alfa AF: 0.0820 Hom.: 101

Bravo AF: 0.108

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.26
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs394241; hg19: chr5-19560531;