rs11640522

Positions:

• chr16-82766763-C-T

Variant summary

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

The NM_001257.5(CDH13):​c.46-91599C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,946 control chromosomes in the GnomAD database, including 4,562 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 0.22 (4562 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH13	NM_001257.5	c.46-91599C>T		intron_variant		ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.46-91599C>T		intron_variant		1	NM_001257.5	ENSP00000479395	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33276 AN: 151828 Hom.: 4559 Cov.: 32

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.219 AC: 33283 AN: 151946 Hom.: 4562 Cov.: 32 AF XY: 0.224 AC XY: 16616 AN XY: 74228

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.230

Alfa AF: 0.264 Hom.: 11109

Bravo AF: 0.213

Asia WGS AF: 0.252 AC: 878 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	8.8
DANN	Benign	0.73

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: rs11640522; hg19: chr16-82800368;