16-82799344-C-T

Variant names:

• chr16-82799344-C-T
• rs4598906
• NM_001257.5:c.46-59018C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001257.5(CDH13):​c.46-59018C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,092 control chromosomes in the GnomAD database, including 7,684 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 (7684 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.46-59018C>T		intron_variant	Intron 1 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.46-59018C>T		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44214 AN: 151974 Hom.: 7688 Cov.: 32

Gnomad AFR AF: 0.0976

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.291 AC: 44214 AN: 152092 Hom.: 7684 Cov.: 32 AF XY: 0.294 AC XY: 21852 AN XY: 74362

African (AFR) AF: 0.0974 AC: 4041 AN: 41508

American (AMR) AF: 0.369 AC: 5645 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1111 AN: 3464

East Asian (EAS) AF: 0.243 AC: 1256 AN: 5172

South Asian (SAS) AF: 0.434 AC: 2087 AN: 4812

European-Finnish (FIN) AF: 0.366 AC: 3864 AN: 10566

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25181 AN: 67968

Other (OTH) AF: 0.306 AC: 647 AN: 2116

Alfa AF: 0.334 Hom.: 24928

Bravo AF: 0.278

Asia WGS AF: 0.301 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Benign	0.55
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: rs4598906; hg19: chr16-82832949;