NM_001257.5:c.636+46159T>G

Variant names:

• chr16-83263656-T-G
• rs16960006
• NM_001257.5:c.636+46159T>G

Variant summary

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

The NM_001257.5(CDH13):​c.636+46159T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 152,296 control chromosomes in the GnomAD database, including 485 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 0.072 (485 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	NM_001257.5	MANE Select	c.636+46159T>G		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.777+46159T>G		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.519+46159T>G		intron	N/A	NP_001207418.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.636+46159T>G		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000268613.14	TSL:2	c.777+46159T>G		intron	N/A	ENSP00000268613.10
	CDH13	ENST00000428848.7	TSL:2	c.519+46159T>G		intron	N/A	ENSP00000394557.3

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10876 AN: 152178 Hom.: 484 Cov.: 33

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.0869

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

GnomAD4 genome AF: 0.0715 AC: 10892 AN: 152296 Hom.: 485 Cov.: 33 AF XY: 0.0717 AC XY: 5338 AN XY: 74488

African (AFR) AF: 0.0522 AC: 2170 AN: 41560

American (AMR) AF: 0.110 AC: 1677 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1015 AN: 5174

South Asian (SAS) AF: 0.117 AC: 563 AN: 4828

European-Finnish (FIN) AF: 0.0203 AC: 216 AN: 10622

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0703 AC: 4781 AN: 68012

Other (OTH) AF: 0.0870 AC: 184 AN: 2116

Alfa AF: 0.0753 Hom.: 1310

Bravo AF: 0.0782

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.54
PhyloP100		-0.62
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: rs16960006; hg19: chr16-83297261;