16-83315219-A-G

Position:

• chr16-83315219-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CDH13	NM_001257.5	c.637-29643A>G		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.637-29643A>G		intron_variant		1	NM_001257.5	P1

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

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.329

Alfa AF: 0.317 Hom.: 15343

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1035569; hg19: chr16-83348824;