rs12598842

Variant names:

• chr16-83554349-A-G
• rs12598842
• NM_001257.5:c.961-48105A>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.961-48105A>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 151,978 control chromosomes in the GnomAD database, including 8,274 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 (8274 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.961-48105A>G		intron_variant	Intron 7 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.961-48105A>G		intron_variant	Intron 7 of 13	1	NM_001257.5	ENSP00000479395.1
CDH13	ENST00000268613.14	c.1102-48105A>G		intron_variant	Intron 8 of 14	2		ENSP00000268613.10
CDH13	ENST00000428848.7	c.844-48105A>G		intron_variant	Intron 6 of 12	2		ENSP00000394557.3
CDH13	ENST00000539548.6	n.*593-48105A>G		intron_variant	Intron 6 of 12	2		ENSP00000442225.2

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46942 AN: 151862 Hom.: 8264 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.309 AC: 46970 AN: 151978 Hom.: 8274 Cov.: 31 AF XY: 0.313 AC XY: 23276 AN XY: 74270

African (AFR) AF: 0.126 AC: 5228 AN: 41496

American (AMR) AF: 0.372 AC: 5664 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1115 AN: 3472

East Asian (EAS) AF: 0.405 AC: 2084 AN: 5150

South Asian (SAS) AF: 0.289 AC: 1390 AN: 4806

European-Finnish (FIN) AF: 0.444 AC: 4675 AN: 10540

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.378 AC: 25685 AN: 67952

Other (OTH) AF: 0.313 AC: 661 AN: 2114

Alfa AF: 0.357 Hom.: 5382

Bravo AF: 0.298

Asia WGS AF: 0.338 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.60
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12598842; hg19: chr16-83587954;