16-83483368-G-C

Variant names:

• chr16-83483368-G-C
• rs17758876
• NM_001257.5:c.782-3109G>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.782-3109G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0475 in 151,964 control chromosomes in the GnomAD database, including 218 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 0.048 (218 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 0 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 (NFE) allele frequency at 95% confidence interval = 0.0677 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.782-3109G>C		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.923-3109G>C		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.665-3109G>C		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.782-3109G>C		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000268613.14	TSL:2	c.923-3109G>C		intron	N/A	ENSP00000268613.10
	CDH13	ENST00000428848.7	TSL:2	c.665-3109G>C		intron	N/A	ENSP00000394557.3

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7227 AN: 151866 Hom.: 218 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0511

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0411

Gnomad FIN AF: 0.0483

Gnomad MID AF: 0.0705

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0475 AC: 7225 AN: 151964 Hom.: 218 Cov.: 32 AF XY: 0.0467 AC XY: 3468 AN XY: 74252

African (AFR) AF: 0.0113 AC: 466 AN: 41422

American (AMR) AF: 0.0510 AC: 779 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3464

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.0408 AC: 196 AN: 4808

European-Finnish (FIN) AF: 0.0483 AC: 508 AN: 10524

Middle Eastern (MID) AF: 0.0729 AC: 21 AN: 288

European-Non Finnish (NFE) AF: 0.0694 AC: 4717 AN: 67984

Other (OTH) AF: 0.0503 AC: 106 AN: 2108

Alfa AF: 0.0249 Hom.: 12

Bravo AF: 0.0466

Asia WGS AF: 0.0180 AC: 62 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	2.9
DANN	Benign	0.54
PhyloP100		0.34
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: rs17758876; hg19: chr16-83516973;