16-82628663-G-T

Variant names:

• chr16-82628663-G-T
• rs4783244
• NM_001257.5:c.45+1526G>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.45+1526G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,828 control chromosomes in the GnomAD database, including 11,872 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 0.38 (11872 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 49 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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.45+1526G>T		intron_variant	Intron 1 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.45+1526G>T		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57743 AN: 151712 Hom.: 11873 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.380 AC: 57753 AN: 151828 Hom.: 11872 Cov.: 32 AF XY: 0.382 AC XY: 28348 AN XY: 74186

African (AFR) AF: 0.237 AC: 9818 AN: 41416

American (AMR) AF: 0.317 AC: 4833 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1431 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1738 AN: 5138

South Asian (SAS) AF: 0.436 AC: 2091 AN: 4794

European-Finnish (FIN) AF: 0.486 AC: 5121 AN: 10532

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31330 AN: 67898

Other (OTH) AF: 0.380 AC: 800 AN: 2108

Alfa AF: 0.430 Hom.: 50171

Bravo AF: 0.355

Asia WGS AF: 0.368 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.3
DANN	Benign	0.87
PhyloP100		-0.22
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: rs4783244; hg19: chr16-82662268;