rs17674039

chr16-82878769-T-C

Variant summary

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

The NM_001257.5(CDH13):c.157+20296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 151,874 control chromosomes in the GnomAD database, including 1,065 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 0.11 (1065 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443

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 = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.157+20296T>C		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.157+20296T>C		intron_variant		1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17323 AN: 151756 Hom.: 1063 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0820

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.0993

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.114 AC: 17334 AN: 151874 Hom.: 1065 Cov.: 31 AF XY: 0.113 AC XY: 8410 AN XY: 74194

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0818

Gnomad4 ASJ AF: 0.0939

Gnomad4 EAS AF: 0.0235

Gnomad4 SAS AF: 0.0996

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.111

Alfa AF: 0.115 Hom.: 1447

Bravo AF: 0.109

Asia WGS AF: 0.0730 AC: 255 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	1.2
Dann	Benign	0.82

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: rs17674039; hg19: chr16-82912374;