16-82789819-A-G

Variant names:

• chr16-82789819-A-G
• rs8056579
• NM_001257.5:c.46-68543A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257.5(CDH13):​c.46-68543A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,028 control chromosomes in the GnomAD database, including 50,521 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 0.81 (50521 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 8 publications found

Genes affected

CDH13 (HGNC:1753): (cadherin 13) This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation. It also protects vascular endothelial cells from apoptosis due to oxidative stress, and is associated with resistance to atherosclerosis. The gene is hypermethylated in many types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2011]

ENSG00000260862 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257.5. 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
	CDH13	NM_001257.5	MANE Select	c.46-68543A>G		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.187-68543A>G		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.46-68543A>G		intron	N/A	NP_001207418.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.46-68543A>G		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000431540.7	TSL:1	c.46-68543A>G		intron	N/A	ENSP00000408632.3
	CDH13	ENST00000567445.1	TSL:1	c.46-68543A>G		intron	N/A	ENSP00000456297.1

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123543 AN: 151910 Hom.: 50491 Cov.: 31

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.813 AC: 123624 AN: 152028 Hom.: 50521 Cov.: 31 AF XY: 0.817 AC XY: 60706 AN XY: 74308

African (AFR) AF: 0.723 AC: 29959 AN: 41432

American (AMR) AF: 0.859 AC: 13138 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2846 AN: 3464

East Asian (EAS) AF: 0.962 AC: 4962 AN: 5160

South Asian (SAS) AF: 0.864 AC: 4149 AN: 4804

European-Finnish (FIN) AF: 0.837 AC: 8855 AN: 10574

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57025 AN: 67976

Other (OTH) AF: 0.802 AC: 1696 AN: 2114

Alfa AF: 0.831 Hom.: 154261

Bravo AF: 0.809

Asia WGS AF: 0.893 AC: 3104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.49
PhyloP100		-0.16
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: rs8056579; hg19: chr16-82823424;