chr16-83605706-G-A

Variant names:

• chr16-83605706-G-A
• rs8059833
• NM_001257.5:c.1101+3112G>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.1101+3112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,022 control chromosomes in the GnomAD database, including 9,293 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 0.34 (9293 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 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.1101+3112G>A		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.1242+3112G>A		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.984+3112G>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.1101+3112G>A		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000268613.14	TSL:2	c.1242+3112G>A		intron	N/A	ENSP00000268613.10
	CDH13	ENST00000428848.7	TSL:2	c.984+3112G>A		intron	N/A	ENSP00000394557.3

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52129 AN: 151902 Hom.: 9271 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.343 AC: 52197 AN: 152022 Hom.: 9293 Cov.: 32 AF XY: 0.340 AC XY: 25291 AN XY: 74292

African (AFR) AF: 0.405 AC: 16780 AN: 41452

American (AMR) AF: 0.336 AC: 5140 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1142 AN: 3472

East Asian (EAS) AF: 0.183 AC: 944 AN: 5166

South Asian (SAS) AF: 0.296 AC: 1426 AN: 4820

European-Finnish (FIN) AF: 0.319 AC: 3367 AN: 10560

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.325 AC: 22082 AN: 67946

Other (OTH) AF: 0.363 AC: 766 AN: 2112

Alfa AF: 0.332 Hom.: 1264

Bravo AF: 0.351

Asia WGS AF: 0.289 AC: 1006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.78
PhyloP100		0.050
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: rs8059833; hg19: chr16-83639311;