rs4412964

Variant names:

• chr16-83522633-C-T
• rs4412964
• NM_001257.5:c.960+35978C>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.960+35978C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,034 control chromosomes in the GnomAD database, including 12,154 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 0.40 (12154 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 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.960+35978C>T		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.1101+35978C>T		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.843+35978C>T		intron	N/A	NP_001207418.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.960+35978C>T		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000268613.14	TSL:2	c.1101+35978C>T		intron	N/A	ENSP00000268613.10
	CDH13	ENST00000428848.7	TSL:2	c.843+35978C>T		intron	N/A	ENSP00000394557.3

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60260 AN: 151916 Hom.: 12150 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.397 AC: 60289 AN: 152034 Hom.: 12154 Cov.: 32 AF XY: 0.401 AC XY: 29766 AN XY: 74322

African (AFR) AF: 0.450 AC: 18661 AN: 41464

American (AMR) AF: 0.397 AC: 6072 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1371 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2132 AN: 5162

South Asian (SAS) AF: 0.371 AC: 1791 AN: 4822

European-Finnish (FIN) AF: 0.402 AC: 4242 AN: 10550

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24775 AN: 67966

Other (OTH) AF: 0.392 AC: 829 AN: 2114

Alfa AF: 0.368 Hom.: 19481

Bravo AF: 0.396

Asia WGS AF: 0.397 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.59
PhyloP100		-0.38
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: rs4412964; hg19: chr16-83556238;