NM_001257.5:c.637-29643A>G

Variant names:

• chr16-83315219-A-G
• rs1035569
• NM_001257.5:c.637-29643A>G

Variant summary

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

The NM_001257.5(CDH13):​c.637-29643A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,100 control chromosomes in the GnomAD database, including 7,483 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 0.31 (7483 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.637-29643A>G		intron_variant	Intron 5 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.637-29643A>G		intron_variant	Intron 5 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46992 AN: 151982 Hom.: 7473 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.309 AC: 47035 AN: 152100 Hom.: 7483 Cov.: 33 AF XY: 0.310 AC XY: 23021 AN XY: 74320

African (AFR) AF: 0.260 AC: 10786 AN: 41490

American (AMR) AF: 0.371 AC: 5666 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1205 AN: 3468

East Asian (EAS) AF: 0.507 AC: 2623 AN: 5176

South Asian (SAS) AF: 0.298 AC: 1438 AN: 4818

European-Finnish (FIN) AF: 0.275 AC: 2906 AN: 10568

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21385 AN: 67984

Other (OTH) AF: 0.329 AC: 695 AN: 2110

Alfa AF: 0.315 Hom.: 24183

Bravo AF: 0.317

Asia WGS AF: 0.413 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.32
PhyloP100		-1.4
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: rs1035569; hg19: chr16-83348824;