rs1911864

Variant names:

• chr5-19966188-A-G
• rs1911864
• NM_004934.5:c.-257+14872T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004934.5(CDH18):​c.-257+14872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,952 control chromosomes in the GnomAD database, including 26,952 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 0.59 (26952 hom., cov: 32)
• Consequence: CDH18 NM_004934.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.694 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.-257+14872T>C		intron	N/A	NP_004925.1
	CDH18	NM_001291956.3		c.-257+14872T>C		intron	N/A	NP_001278885.1
	CDH18	NM_001349556.2		c.-257+14872T>C		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.-257+14872T>C		intron	N/A	ENSP00000371710.1
	CDH18	ENST00000507958.5	TSL:2	c.-257+14872T>C		intron	N/A	ENSP00000425093.1
	CDH18	ENST00000511273.1	TSL:5	c.-257+21898T>C		intron	N/A	ENSP00000425854.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89954 AN: 151832 Hom.: 26938 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.592 AC: 90022 AN: 151952 Hom.: 26952 Cov.: 32 AF XY: 0.587 AC XY: 43573 AN XY: 74236

African (AFR) AF: 0.657 AC: 27238 AN: 41456

American (AMR) AF: 0.502 AC: 7648 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2308 AN: 3468

East Asian (EAS) AF: 0.713 AC: 3682 AN: 5162

South Asian (SAS) AF: 0.590 AC: 2845 AN: 4824

European-Finnish (FIN) AF: 0.504 AC: 5323 AN: 10554

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38894 AN: 67942

Other (OTH) AF: 0.614 AC: 1296 AN: 2110

Alfa AF: 0.571 Hom.: 4559

Bravo AF: 0.594

Asia WGS AF: 0.643 AC: 2233 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.64
PhyloP100		-0.22
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: rs1911864; hg19: chr5-19966297;