rs11646011

Variant names:

• chr16-82666121-T-C
• rs11646011
• NM_001257.5:c.45+38984T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.94).
• 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 rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.45+38984T>C		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.45+38984T>C		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

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

African (AFR) AF: 0.312 AC: 12904 AN: 41412

American (AMR) AF: 0.268 AC: 4101 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1515 AN: 3470

East Asian (EAS) AF: 0.0453 AC: 234 AN: 5162

South Asian (SAS) AF: 0.305 AC: 1463 AN: 4800

European-Finnish (FIN) AF: 0.482 AC: 5085 AN: 10552

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32803 AN: 67952

Other (OTH) AF: 0.362 AC: 764 AN: 2110

Alfa AF: 0.439 Hom.: 47675

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
PhyloP100		-3.2
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: rs11646011; hg19: chr16-82699726;