18-61380081-A-G

Variant names:

• chr18-61380081-A-G
• rs8088963
• NM_031891.4:c.-153+46254A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031891.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH20	NM_031891.4	MANE Select	c.-153+46254A>G		intron	N/A	NP_114097.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH20	ENST00000262717.9	TSL:2 MANE Select	c.-153+46254A>G		intron	N/A	ENSP00000262717.3	Q9HBT6
	CDH20	ENST00000538374.5	TSL:1	c.-153+45684A>G		intron	N/A	ENSP00000442226.1	Q9HBT6

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

African (AFR) AF: 0.367 AC: 15215 AN: 41502

American (AMR) AF: 0.478 AC: 7305 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1351 AN: 3470

East Asian (EAS) AF: 0.792 AC: 4068 AN: 5138

South Asian (SAS) AF: 0.544 AC: 2620 AN: 4820

European-Finnish (FIN) AF: 0.425 AC: 4498 AN: 10582

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24456 AN: 67966

Other (OTH) AF: 0.379 AC: 799 AN: 2110

Alfa AF: 0.371 Hom.: 18578

Bravo AF: 0.403

Asia WGS AF: 0.641 AC: 2228 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.5
DANN	Benign	0.57
PhyloP100		-0.0040
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: rs8088963; hg19: chr18-59047314;