16-82672521-C-T

Variant names:

• chr16-82672521-C-T
• rs7198915
• NM_001257.5:c.45+45384C>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+45384C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 151,862 control chromosomes in the GnomAD database, including 50,377 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 0.81 (50377 hom., cov: 29)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.45+45384C>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+45384C>T		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123401 AN: 151744 Hom.: 50334 Cov.: 29

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.813 AC: 123502 AN: 151862 Hom.: 50377 Cov.: 29 AF XY: 0.816 AC XY: 60513 AN XY: 74202

African (AFR) AF: 0.856 AC: 35447 AN: 41416

American (AMR) AF: 0.786 AC: 11969 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2674 AN: 3460

East Asian (EAS) AF: 0.698 AC: 3584 AN: 5132

South Asian (SAS) AF: 0.847 AC: 4069 AN: 4806

European-Finnish (FIN) AF: 0.829 AC: 8731 AN: 10532

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54371 AN: 67980

Other (OTH) AF: 0.779 AC: 1635 AN: 2100

Alfa AF: 0.800 Hom.: 204171

Bravo AF: 0.808

Asia WGS AF: 0.800 AC: 2785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.7
DANN	Benign	0.50
PhyloP100		0.23
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: rs7198915; hg19: chr16-82706126;