NM_001257.5:c.46-74716G>A

Variant names:

• chr16-82783646-G-A
• rs11646849
• NM_001257.5:c.46-74716G>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.46-74716G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,060 control chromosomes in the GnomAD database, including 15,934 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 0.45 (15934 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• 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]

ENSG00000260862 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.46-74716G>A		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.46-74716G>A		intron_variant	Intron 1 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67698 AN: 151942 Hom.: 15915 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.446 AC: 67754 AN: 152060 Hom.: 15934 Cov.: 33 AF XY: 0.450 AC XY: 33438 AN XY: 74342

African (AFR) AF: 0.291 AC: 12073 AN: 41492

American (AMR) AF: 0.499 AC: 7623 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1666 AN: 3466

East Asian (EAS) AF: 0.472 AC: 2431 AN: 5154

South Asian (SAS) AF: 0.557 AC: 2689 AN: 4830

European-Finnish (FIN) AF: 0.531 AC: 5611 AN: 10560

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34157 AN: 67954

Other (OTH) AF: 0.451 AC: 954 AN: 2114

Alfa AF: 0.470 Hom.: 3015

Bravo AF: 0.431

Asia WGS AF: 0.467 AC: 1625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.72
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: rs11646849; hg19: chr16-82817251;