NM_001257.5:c.637-19691A>G

Variant names:

• chr16-83325171-A-G
• rs6563898
• NM_001257.5:c.637-19691A>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.637-19691A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,102 control chromosomes in the GnomAD database, including 35,637 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 0.68 (35637 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 8 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.637-19691A>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.637-19691A>G		intron_variant	Intron 5 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103966 AN: 151984 Hom.: 35609 Cov.: 33

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.684 AC: 104037 AN: 152102 Hom.: 35637 Cov.: 33 AF XY: 0.682 AC XY: 50731 AN XY: 74356

African (AFR) AF: 0.708 AC: 29333 AN: 41446

American (AMR) AF: 0.608 AC: 9289 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2356 AN: 3468

East Asian (EAS) AF: 0.556 AC: 2878 AN: 5172

South Asian (SAS) AF: 0.707 AC: 3411 AN: 4826

European-Finnish (FIN) AF: 0.713 AC: 7538 AN: 10572

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46903 AN: 68020

Other (OTH) AF: 0.673 AC: 1421 AN: 2112

Alfa AF: 0.687 Hom.: 28248

Bravo AF: 0.676

Asia WGS AF: 0.611 AC: 2128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.78
DANN	Benign	0.47
PhyloP100		-0.038
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: rs6563898; hg19: chr16-83358776;