rs1895535

Variant names:

• chr16-83239190-A-G
• rs1895535
• NM_001257.5:c.636+21693A>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.636+21693A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 152,210 control chromosomes in the GnomAD database, including 68,352 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 0.95 (68352 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.636+21693A>G		intron_variant	Intron 5 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.636+21693A>G		intron_variant	Intron 5 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.948 AC: 144131 AN: 152092 Hom.: 68307 Cov.: 31

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.950

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

GnomAD4 genome AF: 0.948 AC: 144234 AN: 152210 Hom.: 68352 Cov.: 31 AF XY: 0.948 AC XY: 70559 AN XY: 74400

African (AFR) AF: 0.936 AC: 38862 AN: 41504

American (AMR) AF: 0.966 AC: 14776 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3271 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5160 AN: 5162

South Asian (SAS) AF: 0.959 AC: 4624 AN: 4824

European-Finnish (FIN) AF: 0.953 AC: 10105 AN: 10602

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.945 AC: 64251 AN: 68022

Other (OTH) AF: 0.951 AC: 2012 AN: 2116

Alfa AF: 0.946 Hom.: 82600

Bravo AF: 0.948

Asia WGS AF: 0.976 AC: 3394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.72
PhyloP100		0.081
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: rs1895535; hg19: chr16-83272795;