rs8045006

Positions:

• chr16-83222668-C-A
• chr16-83222668-C-T

Variant summary

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

The ENST00000567109.6(CDH13):​c.636+5171C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 152,000 control chromosomes in the GnomAD database, including 215 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 0.051 (215 hom., cov: 31)
• Consequence: CDH13 ENST00000567109.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH13	NM_001257.5	c.636+5171C>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.636+5171C>A		intron_variant		1	NM_001257.5	ENSP00000479395	P1

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7820 AN: 151882 Hom.: 215 Cov.: 31

Gnomad AFR AF: 0.0631

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.0415

Gnomad SAS AF: 0.0560

Gnomad FIN AF: 0.0376

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0430

Gnomad OTH AF: 0.0433

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

GnomAD4 genome AF: 0.0515 AC: 7825 AN: 152000 Hom.: 215 Cov.: 31 AF XY: 0.0521 AC XY: 3871 AN XY: 74304

Gnomad4 AFR AF: 0.0630

Gnomad4 AMR AF: 0.0625

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.0414

Gnomad4 SAS AF: 0.0556

Gnomad4 FIN AF: 0.0376

Gnomad4 NFE AF: 0.0430

Gnomad4 OTH AF: 0.0428

Alfa AF: 0.0276 Hom.: 26

Bravo AF: 0.0522

Asia WGS AF: 0.0490 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.68

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: rs8045006; hg19: chr16-83256273;