chr16-82766763-C-T

Variant names:

• chr16-82766763-C-T
• rs11640522
• NM_001257.5:c.46-91599C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.46-91599C>T		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.46-91599C>T		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

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

African (AFR) AF: 0.0533 AC: 2211 AN: 41480

American (AMR) AF: 0.344 AC: 5246 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 893 AN: 3468

East Asian (EAS) AF: 0.237 AC: 1224 AN: 5164

South Asian (SAS) AF: 0.368 AC: 1765 AN: 4792

European-Finnish (FIN) AF: 0.279 AC: 2936 AN: 10518

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18292 AN: 67964

Other (OTH) AF: 0.230 AC: 483 AN: 2104

Alfa AF: 0.253 Hom.: 16557

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
PhyloP100		0.33
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: rs11640522; hg19: chr16-82800368;