16-82629683-G-T

Variant names:

• chr16-82629683-G-T
• rs12051272
• NM_001257.5:c.45+2546G>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+2546G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 152,244 control chromosomes in the GnomAD database, including 379 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 0.036 (379 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 50 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	NM_001257.5	MANE Select	c.45+2546G>T		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.80+2546G>T		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.45+2546G>T		intron	N/A	NP_001207418.1	P55290-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.45+2546G>T		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000431540.7	TSL:1	c.45+2546G>T		intron	N/A	ENSP00000408632.3	P55290-2
	CDH13	ENST00000567445.1	TSL:1	c.45+2546G>T		intron	N/A	ENSP00000456297.1	H3BRL7

Frequencies

GnomAD3 genomes AF: 0.0363 AC: 5523 AN: 152126 Hom.: 382 Cov.: 33

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.0282

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

GnomAD4 genome AF: 0.0362 AC: 5514 AN: 152244 Hom.: 379 Cov.: 33 AF XY: 0.0425 AC XY: 3160 AN XY: 74436

African (AFR) AF: 0.0265 AC: 1102 AN: 41548

American (AMR) AF: 0.0266 AC: 407 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.325 AC: 1676 AN: 5152

South Asian (SAS) AF: 0.0760 AC: 367 AN: 4830

European-Finnish (FIN) AF: 0.101 AC: 1073 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0119 AC: 807 AN: 68024

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

Alfa AF: 0.0232 Hom.: 837

Bravo AF: 0.0316

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.8
DANN	Benign	0.52
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs12051272; hg19: chr16-82663288;