chr16-83198607-C-T

Variant names:

• chr16-83198607-C-T
• rs17675933
• NM_001257.5:c.484-18738C>T

Variant summary

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

The NM_001257.5(CDH13):​c.484-18738C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 152,192 control chromosomes in the GnomAD database, including 222 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 0.042 (222 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.484-18738C>T		intron_variant	Intron 4 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.484-18738C>T		intron_variant	Intron 4 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6383 AN: 152074 Hom.: 222 Cov.: 33

Gnomad AFR AF: 0.00949

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0187

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.0331

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

GnomAD4 genome AF: 0.0419 AC: 6384 AN: 152192 Hom.: 222 Cov.: 33 AF XY: 0.0442 AC XY: 3290 AN XY: 74402

African (AFR) AF: 0.00946 AC: 393 AN: 41548

American (AMR) AF: 0.0336 AC: 514 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0187 AC: 90 AN: 4818

European-Finnish (FIN) AF: 0.126 AC: 1335 AN: 10580

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0562 AC: 3823 AN: 67996

Other (OTH) AF: 0.0327 AC: 69 AN: 2108

Alfa AF: 0.0495 Hom.: 114

Bravo AF: 0.0337

Asia WGS AF: 0.0100 AC: 37 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	9.0
DANN	Benign	0.65
PhyloP100		0.021
Mutation Taster		=98/2	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: rs17675933; hg19: chr16-83232212;