16-83034409-G-C

Variant names:

• chr16-83034409-G-C
• rs4366698
• NM_001257.5:c.366+2191G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257.5(CDH13):​c.366+2191G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,126 control chromosomes in the GnomAD database, including 43,631 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 0.75 (43631 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.366+2191G>C		intron_variant	Intron 3 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.366+2191G>C		intron_variant	Intron 3 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114237 AN: 152008 Hom.: 43567 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.752 AC: 114364 AN: 152126 Hom.: 43631 Cov.: 32 AF XY: 0.754 AC XY: 56097 AN XY: 74380

African (AFR) AF: 0.886 AC: 36794 AN: 41506

American (AMR) AF: 0.725 AC: 11076 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2214 AN: 3468

East Asian (EAS) AF: 0.722 AC: 3722 AN: 5154

South Asian (SAS) AF: 0.822 AC: 3963 AN: 4822

European-Finnish (FIN) AF: 0.735 AC: 7787 AN: 10590

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46453 AN: 68000

Other (OTH) AF: 0.724 AC: 1528 AN: 2110

Alfa AF: 0.598 Hom.: 1598

Bravo AF: 0.754

Asia WGS AF: 0.791 AC: 2750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.90
DANN	Benign	0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs4366698; hg19: chr16-83068014;