rs8050316

Positions:

• chr16-82662531-C-A

Variant summary

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

The NM_001257.5(CDH13):​c.45+35394C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,114 control chromosomes in the GnomAD database, including 3,654 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 0.21 (3654 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.992

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH13	NM_001257.5	c.45+35394C>A		intron_variant		ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.45+35394C>A		intron_variant		1	NM_001257.5	ENSP00000479395	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32107 AN: 151996 Hom.: 3650 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.211 AC: 32146 AN: 152114 Hom.: 3654 Cov.: 33 AF XY: 0.211 AC XY: 15722 AN XY: 74354

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.211

Alfa AF: 0.200 Hom.: 867

Bravo AF: 0.216

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.65

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: rs8050316; hg19: chr16-82696136;