16-82900827-C-G

Variant names:

• chr16-82900827-C-G
• rs9646331
• NM_001257.5:c.157+42354C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001257.5(CDH13):​c.157+42354C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,184 control chromosomes in the GnomAD database, including 1,634 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 0.14 (1634 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346
• Publications: 4 publications found

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]

LOC124903733 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.157+42354C>G		intron_variant	Intron 2 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.157+42354C>G		intron_variant	Intron 2 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21292 AN: 152066 Hom.: 1631 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.140 AC: 21316 AN: 152184 Hom.: 1634 Cov.: 33 AF XY: 0.140 AC XY: 10425 AN XY: 74402

African (AFR) AF: 0.187 AC: 7753 AN: 41492

American (AMR) AF: 0.0791 AC: 1209 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 401 AN: 3470

East Asian (EAS) AF: 0.0226 AC: 117 AN: 5184

South Asian (SAS) AF: 0.102 AC: 492 AN: 4822

European-Finnish (FIN) AF: 0.212 AC: 2251 AN: 10602

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8665 AN: 68006

Other (OTH) AF: 0.124 AC: 263 AN: 2116

Alfa AF: 0.0657 Hom.: 70

Bravo AF: 0.133

Asia WGS AF: 0.0760 AC: 265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.65
PhyloP100		0.35
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

Other links and lift over

dbSNP: rs9646331; hg19: chr16-82934432;