NM_001257.5:c.46-101116A>G

Variant names:

• chr16-82757246-A-G
• rs4783266
• NM_001257.5:c.46-101116A>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.46-101116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,120 control chromosomes in the GnomAD database, including 46,667 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 0.78 (46667 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.46-101116A>G		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.46-101116A>G		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118140 AN: 152004 Hom.: 46620 Cov.: 32

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.777 AC: 118241 AN: 152120 Hom.: 46667 Cov.: 32 AF XY: 0.771 AC XY: 57330 AN XY: 74334

African (AFR) AF: 0.919 AC: 38140 AN: 41518

American (AMR) AF: 0.657 AC: 10034 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2602 AN: 3472

East Asian (EAS) AF: 0.800 AC: 4129 AN: 5164

South Asian (SAS) AF: 0.644 AC: 3100 AN: 4810

European-Finnish (FIN) AF: 0.715 AC: 7554 AN: 10572

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.737 AC: 50103 AN: 67988

Other (OTH) AF: 0.759 AC: 1601 AN: 2108

Alfa AF: 0.751 Hom.: 7698

Bravo AF: 0.781

Asia WGS AF: 0.753 AC: 2619 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	3.2
DANN	Benign	0.46
PhyloP100		0.71
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: rs4783266; hg19: chr16-82790851;