rs10514590

Variant names:

• chr16-83615165-C-T
• rs10514590
• NM_001257.5:c.1101+12571C>T

Variant summary

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

The NM_001257.5(CDH13):​c.1101+12571C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 152,032 control chromosomes in the GnomAD database, including 913 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 (913 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.844
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) 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.1101+12571C>T		intron_variant	Intron 8 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.1101+12571C>T		intron_variant	Intron 8 of 13	1	NM_001257.5	ENSP00000479395.1
CDH13	ENST00000268613.14	c.1242+12571C>T		intron_variant	Intron 9 of 14	2		ENSP00000268613.10
CDH13	ENST00000428848.7	c.984+12571C>T		intron_variant	Intron 7 of 12	2		ENSP00000394557.3
CDH13	ENST00000539548.6	n.*733+12571C>T		intron_variant	Intron 7 of 12	2		ENSP00000442225.2

Frequencies

GnomAD3 genomes AF: 0.0785 AC: 11929 AN: 151914 Hom.: 911 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.0234

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0594

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

GnomAD4 genome AF: 0.0785 AC: 11939 AN: 152032 Hom.: 913 Cov.: 32 AF XY: 0.0780 AC XY: 5799 AN XY: 74304

African (AFR) AF: 0.191 AC: 7897 AN: 41434

American (AMR) AF: 0.0670 AC: 1023 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3470

East Asian (EAS) AF: 0.106 AC: 545 AN: 5134

South Asian (SAS) AF: 0.0673 AC: 325 AN: 4826

European-Finnish (FIN) AF: 0.0234 AC: 247 AN: 10576

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0230 AC: 1565 AN: 68006

Other (OTH) AF: 0.0588 AC: 124 AN: 2110

Alfa AF: 0.0416 Hom.: 474

Bravo AF: 0.0878

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.5
DANN	Benign	0.63
PhyloP100		0.84
Mutation Taster		=99/1	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: rs10514590; hg19: chr16-83648770;