NM_001257.5:c.637-17403A>G

Variant names:

• chr16-83327459-A-G
• rs17210599
• NM_001257.5:c.637-17403A>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.637-17403A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0708 in 152,312 control chromosomes in the GnomAD database, including 539 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 0.071 (539 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 1 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]

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 = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.637-17403A>G		intron_variant	Intron 5 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.637-17403A>G		intron_variant	Intron 5 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.0709 AC: 10793 AN: 152194 Hom.: 538 Cov.: 33

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0584

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0463

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0626

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

GnomAD4 genome AF: 0.0708 AC: 10791 AN: 152312 Hom.: 539 Cov.: 33 AF XY: 0.0704 AC XY: 5243 AN XY: 74478

African (AFR) AF: 0.0178 AC: 742 AN: 41584

American (AMR) AF: 0.0583 AC: 892 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0460 AC: 222 AN: 4830

European-Finnish (FIN) AF: 0.112 AC: 1186 AN: 10612

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.108 AC: 7345 AN: 68010

Other (OTH) AF: 0.0624 AC: 132 AN: 2116

Alfa AF: 0.0867 Hom.: 92

Bravo AF: 0.0640

Asia WGS AF: 0.0190 AC: 66 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.2
DANN	Benign	0.62
PhyloP100		2.0
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: rs17210599; hg19: chr16-83361064;