rs9941339

chr16-83105719-A-G

Variant summary

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

The NM_001257.5(CDH13):c.367-19666A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,074 control chromosomes in the GnomAD database, including 25,103 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 0.57 (25103 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.367-19666A>G		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.367-19666A>G		intron_variant		1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86766 AN: 151956 Hom.: 25088 Cov.: 33

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.571 AC: 86824 AN: 152074 Hom.: 25103 Cov.: 33 AF XY: 0.568 AC XY: 42214 AN XY: 74350

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.588

Alfa AF: 0.600 Hom.: 35287

Bravo AF: 0.565

Asia WGS AF: 0.450 AC: 1566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	4.2
Dann	Benign	0.41

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: rs9941339; hg19: chr16-83139324;