16-83322403-T-C

Variant names:

• chr16-83322403-T-C
• rs16960234
• NM_001257.5:c.637-22459T>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.637-22459T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 152,232 control chromosomes in the GnomAD database, including 610 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 0.083 (610 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.637-22459T>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.637-22459T>C		intron_variant	Intron 5 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.0828 AC: 12597 AN: 152114 Hom.: 609 Cov.: 31

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0463

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0697

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

GnomAD4 genome AF: 0.0828 AC: 12599 AN: 152232 Hom.: 610 Cov.: 31 AF XY: 0.0816 AC XY: 6075 AN XY: 74422

African (AFR) AF: 0.0568 AC: 2359 AN: 41536

American (AMR) AF: 0.0650 AC: 993 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5188

South Asian (SAS) AF: 0.0459 AC: 221 AN: 4816

European-Finnish (FIN) AF: 0.112 AC: 1186 AN: 10602

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7414 AN: 68014

Other (OTH) AF: 0.0695 AC: 147 AN: 2116

Alfa AF: 0.0907 Hom.: 1003

Bravo AF: 0.0780

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.093
DANN	Benign	0.40
PhyloP100		-2.1
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: rs16960234; hg19: chr16-83356008;