rs11646011

chr16-82666121-T-C

Variant summary

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

The NM_001257.5(CDH13):c.45+38984T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 151,950 control chromosomes in the GnomAD database, including 12,609 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 0.39 (12609 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.24

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.45+38984T>C		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.45+38984T>C		intron_variant		1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59368 AN: 151832 Hom.: 12597 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.0456

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.391 AC: 59395 AN: 151950 Hom.: 12609 Cov.: 32 AF XY: 0.386 AC XY: 28668 AN XY: 74258

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.0453

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.362

Alfa AF: 0.450 Hom.: 32444

Bravo AF: 0.367

Asia WGS AF: 0.180 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.016
Dann	Benign	0.55

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: rs11646011; hg19: chr16-82699726;