18-61380081-A-G

Position:

• chr18-61380081-A-G

Variant summary

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

The NM_031891.4(CDH20):​c.-153+46254A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,068 control chromosomes in the GnomAD database, including 12,757 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 0.40 (12757 hom., cov: 32)
• Consequence: CDH20 NM_031891.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

Genes affected

CDH20 (HGNC:1760): (cadherin 20) This gene is a type II classical cadherin from the cadherin superfamily and one of three cadherin 7-like genes located in a cluster on chromosome 18. The encoded membrane protein is a calcium dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. Since disturbance of intracellular adhesion is a prerequisite for invasion and metastasis of tumor cells, cadherins are considered prime candidates for tumor suppressor genes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH20	NM_031891.4	c.-153+46254A>G		intron_variant		ENST00000262717.9	NP_114097.2
CDH20	XR_001753186.2	n.398+46254A>G		intron_variant, non_coding_transcript_variant
CDH20	XR_001753187.2	n.398+46254A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH20	ENST00000262717.9	c.-153+46254A>G		intron_variant		2	NM_031891.4	ENSP00000262717	P1
CDH20	ENST00000538374.5	c.-153+45684A>G		intron_variant		1		ENSP00000442226	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60623 AN: 151950 Hom.: 12736 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.399 AC: 60688 AN: 152068 Hom.: 12757 Cov.: 32 AF XY: 0.407 AC XY: 30254 AN XY: 74322

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.379

Alfa AF: 0.370 Hom.: 14556

Bravo AF: 0.403

Asia WGS AF: 0.641 AC: 2228 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.5
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs8088963; hg19: chr18-59047314;