rs995021

Positions:

• chr5-20458796-G-A
• chr5-20458796-G-C
• chr5-20458796-G-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+116666C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,008 control chromosomes in the GnomAD database, including 25,700 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 0.57 (25700 hom., cov: 33)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH18	NM_001291956.3	c.-580+116666C>T		intron_variant			NP_001278885.1
CDH18	NM_001349556.2	c.-434+116666C>T		intron_variant			NP_001336485.1
CDH18	NM_001349558.2	c.-728+116666C>T		intron_variant			NP_001336487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH18	ENST00000507958.5	c.-580+116666C>T		intron_variant		2		ENSP00000425093	P1
CDH18	ENST00000507632.2	n.402+116666C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86843 AN: 151888 Hom.: 25663 Cov.: 33

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.572 AC: 86942 AN: 152008 Hom.: 25700 Cov.: 33 AF XY: 0.565 AC XY: 41987 AN XY: 74294

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.568

Alfa AF: 0.441 Hom.: 1638

Bravo AF: 0.582

Asia WGS AF: 0.432 AC: 1506 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.4
DANN	Benign	0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs995021; hg19: chr5-20458905;