rs8059833

Positions:

• chr16-83605706-G-A
• chr16-83605706-G-T

Variant summary

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

The NM_001257.5(CDH13):​c.1101+3112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,022 control chromosomes in the GnomAD database, including 9,293 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 0.34 (9293 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500

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 = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.1101+3112G>A		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.1101+3112G>A		intron_variant		1	NM_001257.5	P1
CDH13	ENST00000268613.14	c.1242+3112G>A		intron_variant		2
CDH13	ENST00000428848.7	c.984+3112G>A		intron_variant		2
CDH13	ENST00000539548.6	c.*733+3112G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52129 AN: 151902 Hom.: 9271 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.343 AC: 52197 AN: 152022 Hom.: 9293 Cov.: 32 AF XY: 0.340 AC XY: 25291 AN XY: 74292

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.363

Alfa AF: 0.330 Hom.: 1201

Bravo AF: 0.351

Asia WGS AF: 0.289 AC: 1006 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	2.3
DANN	Benign	0.78

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: rs8059833; hg19: chr16-83639311;