NM_001257.5:c.45+80514T>G

Variant names:

• chr16-82707651-T-G
• rs10514564
• NM_001257.5:c.45+80514T>G

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+80514T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,038 control chromosomes in the GnomAD database, including 12,113 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 (12113 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.45+80514T>G		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+80514T>G		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59107 AN: 151920 Hom.: 12108 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.389 AC: 59128 AN: 152038 Hom.: 12113 Cov.: 33 AF XY: 0.396 AC XY: 29426 AN XY: 74322

African (AFR) AF: 0.260 AC: 10764 AN: 41466

American (AMR) AF: 0.449 AC: 6859 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3470

East Asian (EAS) AF: 0.607 AC: 3137 AN: 5166

South Asian (SAS) AF: 0.477 AC: 2296 AN: 4818

European-Finnish (FIN) AF: 0.445 AC: 4700 AN: 10558

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.422 AC: 28654 AN: 67976

Other (OTH) AF: 0.380 AC: 800 AN: 2108

Alfa AF: 0.411 Hom.: 54956

Bravo AF: 0.381

Asia WGS AF: 0.524 AC: 1822 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	1.5
DANN	Benign	0.66
PhyloP100		-0.16
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: rs10514564; hg19: chr16-82741256;