chr16-82659207-T-C

Variant names:

• chr16-82659207-T-C
• rs8057927
• NM_001257.5:c.45+32070T>C

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+32070T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,238 control chromosomes in the GnomAD database, including 1,455 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 0.12 (1455 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 13 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 (EAS) allele frequency at 95% confidence interval = 0.25 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+32070T>C		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.186+19742T>C		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.45+32070T>C		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+32070T>C		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000431540.7	TSL:1	c.45+32070T>C		intron	N/A	ENSP00000408632.3	P55290-2
	CDH13	ENST00000567445.1	TSL:1	c.45+32070T>C		intron	N/A	ENSP00000456297.1	H3BRL7

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17934 AN: 152120 Hom.: 1442 Cov.: 33

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.0934

Gnomad FIN AF: 0.0598

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0666

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.118 AC: 17975 AN: 152238 Hom.: 1455 Cov.: 33 AF XY: 0.118 AC XY: 8794 AN XY: 74430

African (AFR) AF: 0.212 AC: 8818 AN: 41514

American (AMR) AF: 0.110 AC: 1690 AN: 15306

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

East Asian (EAS) AF: 0.261 AC: 1349 AN: 5162

South Asian (SAS) AF: 0.0927 AC: 447 AN: 4824

European-Finnish (FIN) AF: 0.0598 AC: 635 AN: 10618

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0666 AC: 4533 AN: 68024

Other (OTH) AF: 0.101 AC: 214 AN: 2114

Alfa AF: 0.0878 Hom.: 2497

Bravo AF: 0.126

Asia WGS AF: 0.176 AC: 612 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	3.6
DANN	Benign	0.37
PhyloP100		0.23
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: rs8057927; hg19: chr16-82692812;