NM_001257.5:c.45+11585C>T

Variant names:

• chr16-82638722-C-T
• rs12922394
• NM_001257.5:c.45+11585C>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.45+11585C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 150,940 control chromosomes in the GnomAD database, including 1,290 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 0.11 (1290 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487
• Publications: 18 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.45+11585C>T		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.45+11585C>T		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17185 AN: 150818 Hom.: 1287 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.0547

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0595

Gnomad OTH AF: 0.0883

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

GnomAD4 genome AF: 0.114 AC: 17205 AN: 150940 Hom.: 1290 Cov.: 32 AF XY: 0.115 AC XY: 8479 AN XY: 73798

African (AFR) AF: 0.215 AC: 8836 AN: 41008

American (AMR) AF: 0.0838 AC: 1271 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.0547 AC: 188 AN: 3440

East Asian (EAS) AF: 0.221 AC: 1138 AN: 5158

South Asian (SAS) AF: 0.102 AC: 487 AN: 4776

European-Finnish (FIN) AF: 0.101 AC: 1060 AN: 10492

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0594 AC: 4017 AN: 67606

Other (OTH) AF: 0.0883 AC: 185 AN: 2094

Alfa AF: 0.0771 Hom.: 2731

Bravo AF: 0.117

Asia WGS AF: 0.165 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.49
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: rs12922394; hg19: chr16-82672327;