16-83111745-G-A

Variant names:

• chr16-83111745-G-A
• rs4508407
• NM_001257.5:c.367-13640G>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.367-13640G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,016 control chromosomes in the GnomAD database, including 29,792 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 0.62 (29792 hom., cov: 32)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.367-13640G>A		intron_variant	Intron 3 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.367-13640G>A		intron_variant	Intron 3 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94168 AN: 151900 Hom.: 29760 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.620 AC: 94250 AN: 152016 Hom.: 29792 Cov.: 32 AF XY: 0.614 AC XY: 45618 AN XY: 74284

African (AFR) AF: 0.633 AC: 26223 AN: 41448

American (AMR) AF: 0.503 AC: 7690 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2326 AN: 3470

East Asian (EAS) AF: 0.324 AC: 1675 AN: 5162

South Asian (SAS) AF: 0.436 AC: 2094 AN: 4806

European-Finnish (FIN) AF: 0.673 AC: 7115 AN: 10566

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45151 AN: 67956

Other (OTH) AF: 0.615 AC: 1301 AN: 2114

Alfa AF: 0.644 Hom.: 123832

Bravo AF: 0.610

Asia WGS AF: 0.419 AC: 1459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.32
DANN	Benign	0.63
PhyloP100		-1.1
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: rs4508407; hg19: chr16-83145350;