18-61360830-A-G

Variant names:

• chr18-61360830-A-G
• rs11664910
• NM_031891.4:c.-153+27003A>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+27003A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,158 control chromosomes in the GnomAD database, including 6,921 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 0.29 (6921 hom., cov: 33)
• Consequence: CDH20 NM_031891.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH20	NM_031891.4	MANE Select	c.-153+27003A>G		intron	N/A	NP_114097.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH20	ENST00000262717.9	TSL:2 MANE Select	c.-153+27003A>G		intron	N/A	ENSP00000262717.3
	CDH20	ENST00000538374.5	TSL:1	c.-153+26433A>G		intron	N/A	ENSP00000442226.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43574 AN: 152040 Hom.: 6919 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.286 AC: 43578 AN: 152158 Hom.: 6921 Cov.: 33 AF XY: 0.279 AC XY: 20776 AN XY: 74362

African (AFR) AF: 0.166 AC: 6895 AN: 41540

American (AMR) AF: 0.288 AC: 4411 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1234 AN: 3470

East Asian (EAS) AF: 0.136 AC: 701 AN: 5164

South Asian (SAS) AF: 0.272 AC: 1312 AN: 4824

European-Finnish (FIN) AF: 0.277 AC: 2929 AN: 10580

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24826 AN: 67968

Other (OTH) AF: 0.324 AC: 685 AN: 2116

Alfa AF: 0.286 Hom.: 2590

Bravo AF: 0.280

Asia WGS AF: 0.184 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.61
PhyloP100		1.4
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: rs11664910; hg19: chr18-59028063;