rs4782726

Variant names:

• chr16-82667728-A-G
• rs4782726
• NM_001257.5:c.45+40591A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-82667728-A-G
• chr16-82667728-A-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+40591A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 151,846 control chromosomes in the GnomAD database, including 47,069 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 0.78 (47069 hom., cov: 29)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 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+40591A>G		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.186+28263A>G		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.45+40591A>G		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+40591A>G		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000431540.7	TSL:1	c.45+40591A>G		intron	N/A	ENSP00000408632.3	P55290-2
	CDH13	ENST00000567445.1	TSL:1	c.45+40591A>G		intron	N/A	ENSP00000456297.1	H3BRL7

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118827 AN: 151728 Hom.: 47041 Cov.: 29

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.783 AC: 118901 AN: 151846 Hom.: 47069 Cov.: 29 AF XY: 0.783 AC XY: 58131 AN XY: 74204

African (AFR) AF: 0.671 AC: 27724 AN: 41346

American (AMR) AF: 0.813 AC: 12398 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2863 AN: 3470

East Asian (EAS) AF: 0.946 AC: 4855 AN: 5132

South Asian (SAS) AF: 0.814 AC: 3912 AN: 4806

European-Finnish (FIN) AF: 0.808 AC: 8537 AN: 10562

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55967 AN: 67970

Other (OTH) AF: 0.774 AC: 1631 AN: 2106

Alfa AF: 0.812 Hom.: 98525

Bravo AF: 0.777

Asia WGS AF: 0.869 AC: 3022 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0020
DANN	Benign	0.51
PhyloP100		-1.7
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: rs4782726; hg19: chr16-82701333;