16-82692121-A-G

Variant names:

• chr16-82692121-A-G
• rs13336758
• NM_001257.5:c.45+64984A>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.45+64984A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,268 control chromosomes in the GnomAD database, including 1,475 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 0.13 (1475 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 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.45+64984A>G		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.186+52656A>G		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.45+64984A>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.45+64984A>G		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000431540.7	TSL:1	c.45+64984A>G		intron	N/A	ENSP00000408632.3
	CDH13	ENST00000567445.1	TSL:1	c.45+64984A>G		intron	N/A	ENSP00000456297.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20215 AN: 152150 Hom.: 1471 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.133 AC: 20229 AN: 152268 Hom.: 1475 Cov.: 33 AF XY: 0.135 AC XY: 10017 AN XY: 74454

African (AFR) AF: 0.160 AC: 6631 AN: 41532

American (AMR) AF: 0.120 AC: 1841 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3464

East Asian (EAS) AF: 0.0623 AC: 323 AN: 5188

South Asian (SAS) AF: 0.125 AC: 602 AN: 4828

European-Finnish (FIN) AF: 0.187 AC: 1987 AN: 10610

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8051 AN: 68020

Other (OTH) AF: 0.135 AC: 286 AN: 2116

Alfa AF: 0.0788 Hom.: 145

Bravo AF: 0.127

Asia WGS AF: 0.108 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.70
PhyloP100		0.088
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: rs13336758; hg19: chr16-82725726;