16-83237838-A-C

Variant names:

• chr16-83237838-A-C
• rs11860907
• NM_001257.5:c.636+20341A>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.636+20341A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,116 control chromosomes in the GnomAD database, including 12,569 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 0.40 (12569 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 8 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.636+20341A>C		intron_variant	Intron 5 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.636+20341A>C		intron_variant	Intron 5 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61185 AN: 151998 Hom.: 12563 Cov.: 33

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.402 AC: 61223 AN: 152116 Hom.: 12569 Cov.: 33 AF XY: 0.401 AC XY: 29793 AN XY: 74354

African (AFR) AF: 0.466 AC: 19331 AN: 41500

American (AMR) AF: 0.306 AC: 4686 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1007 AN: 3468

East Asian (EAS) AF: 0.262 AC: 1356 AN: 5170

South Asian (SAS) AF: 0.335 AC: 1611 AN: 4816

European-Finnish (FIN) AF: 0.443 AC: 4682 AN: 10574

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.403 AC: 27389 AN: 67974

Other (OTH) AF: 0.371 AC: 784 AN: 2114

Alfa AF: 0.391 Hom.: 20024

Bravo AF: 0.395

Asia WGS AF: 0.310 AC: 1081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.3
DANN	Benign	0.34
PhyloP100		-0.21
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: rs11860907; hg19: chr16-83271443;