rs8047176

Positions:

• chr16-83115610-C-G

Variant summary

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

The NM_001257.5(CDH13):​c.367-9775C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,182 control chromosomes in the GnomAD database, including 5,161 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 0.24 (5161 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH13	NM_001257.5	c.367-9775C>G		intron_variant		ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.367-9775C>G		intron_variant		1	NM_001257.5	ENSP00000479395	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36562 AN: 152064 Hom.: 5154 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0633

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.241 AC: 36617 AN: 152182 Hom.: 5161 Cov.: 33 AF XY: 0.242 AC XY: 17985 AN XY: 74404

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0635

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.193

Alfa AF: 0.221 Hom.: 521

Bravo AF: 0.237

Asia WGS AF: 0.113 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.63

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: rs8047176; hg19: chr16-83149215;