rs8057458

Positions:

• chr16-83026546-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.158-5464C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 151,964 control chromosomes in the GnomAD database, including 941 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 0.10 (941 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.158-5464C>G		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.158-5464C>G		intron_variant		1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15459 AN: 151846 Hom.: 941 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0817

Gnomad ASJ AF: 0.0945

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0578

Gnomad FIN AF: 0.0554

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.0897

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

GnomAD4 genome AF: 0.102 AC: 15467 AN: 151964 Hom.: 941 Cov.: 33 AF XY: 0.0984 AC XY: 7306 AN XY: 74270

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0816

Gnomad4 ASJ AF: 0.0945

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0577

Gnomad4 FIN AF: 0.0554

Gnomad4 NFE AF: 0.0874

Gnomad4 OTH AF: 0.0888

Alfa AF: 0.0927 Hom.: 94

Bravo AF: 0.106

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.094
DANN	Benign	0.42

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: rs8057458; hg19: chr16-83060151;