chr16-83290029-G-A

Variant names:

• chr16-83290029-G-A
• rs1862831
• NM_001257.5:c.637-54833G>A

Variant summary

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

The NM_001257.5(CDH13):​c.637-54833G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,886 control chromosomes in the GnomAD database, including 27,609 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 0.59 (27609 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 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.637-54833G>A		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.778-54833G>A		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.520-54833G>A		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.637-54833G>A		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000268613.14	TSL:2	c.778-54833G>A		intron	N/A	ENSP00000268613.10
	CDH13	ENST00000428848.7	TSL:2	c.520-54833G>A		intron	N/A	ENSP00000394557.3

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89417 AN: 151768 Hom.: 27602 Cov.: 31

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.589 AC: 89441 AN: 151886 Hom.: 27609 Cov.: 31 AF XY: 0.593 AC XY: 43968 AN XY: 74176

African (AFR) AF: 0.385 AC: 15954 AN: 41414

American (AMR) AF: 0.652 AC: 9969 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2489 AN: 3472

East Asian (EAS) AF: 0.753 AC: 3862 AN: 5130

South Asian (SAS) AF: 0.717 AC: 3437 AN: 4796

European-Finnish (FIN) AF: 0.659 AC: 6946 AN: 10534

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44599 AN: 67940

Other (OTH) AF: 0.623 AC: 1315 AN: 2112

Alfa AF: 0.640 Hom.: 38859

Bravo AF: 0.578

Asia WGS AF: 0.717 AC: 2489 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.30
PhyloP100		-0.31
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: rs1862831; hg19: chr16-83323634;