16-82778949-G-T

Variant names:

• chr16-82778949-G-T
• rs17276565
• NM_001257.5:c.46-79413G>T

Variant summary

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

The NM_001257.5(CDH13):​c.46-79413G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 152,156 control chromosomes in the GnomAD database, including 621 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 0.079 (621 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• 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]

ENSG00000260862 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.46-79413G>T		intron_variant	Intron 1 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.46-79413G>T		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.0794 AC: 12076 AN: 152038 Hom.: 620 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.00694

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0794 AC: 12075 AN: 152156 Hom.: 621 Cov.: 32 AF XY: 0.0781 AC XY: 5807 AN XY: 74372

African (AFR) AF: 0.0283 AC: 1177 AN: 41536

American (AMR) AF: 0.0855 AC: 1305 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3466

East Asian (EAS) AF: 0.00696 AC: 36 AN: 5174

South Asian (SAS) AF: 0.130 AC: 627 AN: 4818

European-Finnish (FIN) AF: 0.0808 AC: 855 AN: 10584

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7303 AN: 67992

Other (OTH) AF: 0.106 AC: 225 AN: 2116

Alfa AF: 0.0975 Hom.: 2007

Bravo AF: 0.0775

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.63
PhyloP100		0.014
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: rs17276565; hg19: chr16-82812554; COSMIC: COSV104573910;