rs10514578

Variant names:

• chr16-83326206-G-A
• rs10514578
• NM_001257.5:c.637-18656G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257.5(CDH13):​c.637-18656G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 151,890 control chromosomes in the GnomAD database, including 655 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 0.079 (655 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.637-18656G>A		intron_variant	Intron 5 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.637-18656G>A		intron_variant	Intron 5 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 11974 AN: 151772 Hom.: 654 Cov.: 31

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.0615

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.0452

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0681

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

GnomAD4 genome AF: 0.0788 AC: 11974 AN: 151890 Hom.: 655 Cov.: 31 AF XY: 0.0783 AC XY: 5811 AN XY: 74224

African (AFR) AF: 0.0241 AC: 997 AN: 41444

American (AMR) AF: 0.0635 AC: 969 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0615 AC: 213 AN: 3466

East Asian (EAS) AF: 0.000775 AC: 4 AN: 5164

South Asian (SAS) AF: 0.0448 AC: 215 AN: 4796

European-Finnish (FIN) AF: 0.132 AC: 1385 AN: 10496

Middle Eastern (MID) AF: 0.0377 AC: 11 AN: 292

European-Non Finnish (NFE) AF: 0.118 AC: 7991 AN: 67962

Other (OTH) AF: 0.0679 AC: 143 AN: 2106

Alfa AF: 0.0938 Hom.: 109

Bravo AF: 0.0709

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.4
DANN	Benign	0.73
PhyloP100		0.64
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: rs10514578; hg19: chr16-83359811;