NM_001257.5:c.637-18719T>C

Variant names:

• chr16-83326143-T-C
• rs12325503
• NM_001257.5:c.637-18719T>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.637-18719T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 152,272 control chromosomes in the GnomAD database, including 654 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 0.079 (654 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.637-18719T>C		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.637-18719T>C		intron_variant	Intron 5 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.0788 AC: 11987 AN: 152154 Hom.: 653 Cov.: 32

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0674

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

GnomAD4 genome AF: 0.0787 AC: 11987 AN: 152272 Hom.: 654 Cov.: 32 AF XY: 0.0782 AC XY: 5816 AN XY: 74420

African (AFR) AF: 0.0240 AC: 1000 AN: 41582

American (AMR) AF: 0.0634 AC: 970 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 213 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0446 AC: 215 AN: 4824

European-Finnish (FIN) AF: 0.131 AC: 1384 AN: 10584

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8002 AN: 68016

Other (OTH) AF: 0.0672 AC: 142 AN: 2114

Alfa AF: 0.0857 Hom.: 111

Bravo AF: 0.0710

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.63
PhyloP100		0.36
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: rs12325503; hg19: chr16-83359748;