16-82954267-T-G

Variant names:

• chr16-82954267-T-G
• rs11639621
• NM_001257.5:c.158-77743T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001257.5(CDH13):​c.158-77743T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,850 control chromosomes in the GnomAD database, including 24,721 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 0.55 (24713 hom., cov: 30)
  • Exomes 𝑓: 0.48 (8 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530

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]

ENSG00000260832 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH13	NM_001257.5	c.158-77743T>G		intron_variant	Intron 2 of 13	ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.158-77743T>G		intron_variant	Intron 2 of 13	1	NM_001257.5	ENSP00000479395.1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83786 AN: 151680 Hom.: 24690 Cov.: 30

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.583

GnomAD4 exome AF: 0.481 AC: 25 AN: 52 Hom.: 8 Cov.: 0 AF XY: 0.421 AC XY: 16 AN XY: 38

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.452

GnomAD4 genome AF: 0.552 AC: 83842 AN: 151798 Hom.: 24713 Cov.: 30 AF XY: 0.564 AC XY: 41847 AN XY: 74158

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.581

Alfa AF: 0.533 Hom.: 4557

Bravo AF: 0.547

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs11639621; hg19: chr16-82987872;