5-20485637-A-C

Position:

• chr5-20485637-A-C

Variant summary

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

The NM_001291956.3(CDH18):​c.-580+89825T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,048 control chromosomes in the GnomAD database, including 3,217 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 0.18 (3217 hom., cov: 32)
• Consequence: CDH18 NM_001291956.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH18	NM_001291956.3	c.-580+89825T>G		intron_variant			NP_001278885.1
CDH18	NM_001349556.2	c.-434+89825T>G		intron_variant			NP_001336485.1
CDH18	NM_001349558.2	c.-728+89825T>G		intron_variant			NP_001336487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH18	ENST00000507958.5	c.-580+89825T>G		intron_variant		2		ENSP00000425093	P1
CDH18	ENST00000507632.2	n.402+89825T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28058 AN: 151930 Hom.: 3221 Cov.: 32

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.184 AC: 28048 AN: 152048 Hom.: 3217 Cov.: 32 AF XY: 0.194 AC XY: 14409 AN XY: 74304

Gnomad4 AFR AF: 0.0708

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.195

Alfa AF: 0.191 Hom.: 722

Bravo AF: 0.181

Asia WGS AF: 0.343 AC: 1190 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.23
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12652510; hg19: chr5-20485746;