rs1870847

Variant names:

• chr16-82758864-T-C
• rs1870847
• NM_001257.5:c.46-99498T>C

Variant summary

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

The NM_001257.5(CDH13):​c.46-99498T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,216 control chromosomes in the GnomAD database, including 1,866 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 0.14 (1866 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.46-99498T>C		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.46-99498T>C		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21710 AN: 152098 Hom.: 1866 Cov.: 32

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0874

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.143 AC: 21706 AN: 152216 Hom.: 1866 Cov.: 32 AF XY: 0.138 AC XY: 10240 AN XY: 74420

African (AFR) AF: 0.0653 AC: 2712 AN: 41562

American (AMR) AF: 0.146 AC: 2231 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3468

East Asian (EAS) AF: 0.0878 AC: 454 AN: 5172

South Asian (SAS) AF: 0.134 AC: 646 AN: 4822

European-Finnish (FIN) AF: 0.125 AC: 1327 AN: 10584

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12925 AN: 68006

Other (OTH) AF: 0.182 AC: 385 AN: 2110

Alfa AF: 0.171 Hom.: 1342

Bravo AF: 0.143

Asia WGS AF: 0.119 AC: 414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.68
DANN	Benign	0.39
PhyloP100		-0.34
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: rs1870847; hg19: chr16-82792469;