16-82858291-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001257.5(CDH13):c.46-71G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 962,458 control chromosomes in the GnomAD database, including 6,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1000 hom., cov: 33)
  • Exomes 𝑓: 0.11 (5622 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.285

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 16-82858291-G-A is Benign according to our data. Variant chr16-82858291-G-A is described in ClinVar as [Benign]. Clinvar id is 1241506.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.46-71G>A		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.46-71G>A		intron_variant		1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17144 AN: 152054 Hom.: 993 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.0565

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.111 AC: 90174 AN: 810286 Hom.: 5622 AF XY: 0.111 AC XY: 46545 AN XY: 417518

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.0729

Gnomad4 EAS exome AF: 0.0573

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.113 AC: 17168 AN: 152172 Hom.: 1000 Cov.: 33 AF XY: 0.115 AC XY: 8585 AN XY: 74404

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.0752

Gnomad4 EAS AF: 0.0564

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.106

Alfa AF: 0.110 Hom.: 434

Bravo AF: 0.116

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	8.4
Dann	Benign	0.73

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: rs17740895; hg19: chr16-82891896;