rs1684835

Variant names:

• chr5-19554762-C-T
• rs1684835
• NM_004934.5:c.1254-10757G>A

Variant summary

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

The ENST00000382275.6(CDH18):​c.1254-10757G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 151,952 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: 32)
• Consequence: CDH18 ENST00000382275.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 2 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=-0.94).
• 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: ENST00000382275.6. 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.1254-10757G>A		intron	N/A	NP_004925.1
	CDH18	NM_001291956.3		c.1254-10757G>A		intron	N/A	NP_001278885.1
	CDH18	NM_001349556.2		c.1254-10757G>A		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.1254-10757G>A		intron	N/A	ENSP00000371710.1
	CDH18	ENST00000274170.8	TSL:1	c.1254-10757G>A		intron	N/A	ENSP00000274170.3
	CDH18	ENST00000506372.5	TSL:1	c.1254-10757G>A		intron	N/A	ENSP00000424931.1

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15036 AN: 151834 Hom.: 1029 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0862

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.0964

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.0475

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0593

Gnomad OTH AF: 0.0970

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

GnomAD4 genome AF: 0.0992 AC: 15080 AN: 151952 Hom.: 1040 Cov.: 32 AF XY: 0.0980 AC XY: 7279 AN XY: 74254

African (AFR) AF: 0.195 AC: 8056 AN: 41388

American (AMR) AF: 0.0865 AC: 1320 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3468

East Asian (EAS) AF: 0.0961 AC: 495 AN: 5152

South Asian (SAS) AF: 0.0441 AC: 213 AN: 4826

European-Finnish (FIN) AF: 0.0475 AC: 502 AN: 10576

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

European-Non Finnish (NFE) AF: 0.0593 AC: 4029 AN: 67962

Other (OTH) AF: 0.0970 AC: 205 AN: 2114

Alfa AF: 0.0837 Hom.: 128

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	-0.94
CADD	Benign	0.48
DANN	Benign	0.22
PhyloP100		-0.36
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: rs1684835; hg19: chr5-19554871;