rs11644424

chr16-83292454-C-Achr16-83292454-C-Gchr16-83292454-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257.5(CDH13):c.637-52408C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,936 control chromosomes in the GnomAD database, including 14,225 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 0.42 (14225 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.637-52408C>A		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.637-52408C>A		intron_variant		1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63266 AN: 151818 Hom.: 14227 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.416 AC: 63267 AN: 151936 Hom.: 14225 Cov.: 32 AF XY: 0.422 AC XY: 31371 AN XY: 74256

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.425

Alfa AF: 0.464 Hom.: 21568

Bravo AF: 0.401

Asia WGS AF: 0.544 AC: 1891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.1
Dann	Benign	0.36

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: rs11644424; hg19: chr16-83326059;