rs10061119

Positions:

• chr5-20464409-A-T

Variant summary

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

The NM_001291956.3(CDH18):​c.-580+111053T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 151,982 control chromosomes in the GnomAD database, including 47,232 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 0.79 (47232 hom., cov: 32)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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 (AMR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH18	NM_001291956.3	c.-580+111053T>A		intron_variant
CDH18	NM_001349556.2	c.-434+111053T>A		intron_variant
CDH18	NM_001349558.2	c.-728+111053T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH18	ENST00000507958.5	c.-580+111053T>A		intron_variant		2		P1
CDH18	ENST00000507632.2	n.402+111053T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119408 AN: 151864 Hom.: 47179 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.786 AC: 119517 AN: 151982 Hom.: 47232 Cov.: 32 AF XY: 0.789 AC XY: 58615 AN XY: 74264

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.759

Gnomad4 OTH AF: 0.808

Alfa AF: 0.761 Hom.: 5481

Bravo AF: 0.795

Asia WGS AF: 0.780 AC: 2714 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	0.36
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10061119; hg19: chr5-20464518;