rs10514585

chr16-83250733-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257.5(CDH13):c.636+33236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,042 control chromosomes in the GnomAD database, including 5,252 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 0.26 (5252 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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

Verdict is Benign. Variant got -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 = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.636+33236G>A		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.636+33236G>A		intron_variant		1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39420 AN: 151924 Hom.: 5244 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.259 AC: 39439 AN: 152042 Hom.: 5252 Cov.: 32 AF XY: 0.262 AC XY: 19485 AN XY: 74344

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.260

Alfa AF: 0.246 Hom.: 9337

Bravo AF: 0.264

Asia WGS AF: 0.294 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.3
Dann	Benign	0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs10514585; hg19: chr16-83284338;