chr16-82982045-A-C

Variant names:

• chr16-82982045-A-C
• rs4782742
• NM_001257.5:c.158-49965A>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.158-49965A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,996 control chromosomes in the GnomAD database, including 14,338 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 0.43 (14338 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• 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]

ENSG00000260832 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.158-49965A>C		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.158-49965A>C		intron_variant	Intron 2 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65285 AN: 151878 Hom.: 14303 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.430 AC: 65364 AN: 151996 Hom.: 14338 Cov.: 32 AF XY: 0.437 AC XY: 32478 AN XY: 74290

African (AFR) AF: 0.363 AC: 15029 AN: 41456

American (AMR) AF: 0.492 AC: 7514 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1018 AN: 3472

East Asian (EAS) AF: 0.456 AC: 2355 AN: 5162

South Asian (SAS) AF: 0.475 AC: 2290 AN: 4820

European-Finnish (FIN) AF: 0.564 AC: 5956 AN: 10556

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29737 AN: 67948

Other (OTH) AF: 0.413 AC: 873 AN: 2114

Alfa AF: 0.414 Hom.: 8174

Bravo AF: 0.421

Asia WGS AF: 0.434 AC: 1510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0060
DANN	Benign	0.62
PhyloP100		-1.8
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: rs4782742; hg19: chr16-83015650;