16-82911946-G-C

Position:

• chr16-82911946-G-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+53473G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 151,574 control chromosomes in the GnomAD database, including 43,826 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 0.76 (43826 hom., cov: 29)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.810

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]

CDH13 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH13	NM_001257.5	c.157+53473G>C		intron_variant		ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.157+53473G>C		intron_variant		1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115136 AN: 151458 Hom.: 43794 Cov.: 29

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.760 AC: 115221 AN: 151574 Hom.: 43826 Cov.: 29 AF XY: 0.761 AC XY: 56349 AN XY: 74006

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.759

Alfa AF: 0.760 Hom.: 5444

Bravo AF: 0.758

Asia WGS AF: 0.810 AC: 2817 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.61
DANN	Benign	0.74

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: rs7199677; hg19: chr16-82945551;