16-83779906-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.1682-62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,063,740 control chromosomes in the GnomAD database, including 39,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5406 hom., cov: 32)
  • Exomes 𝑓: 0.25 (34322 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.48

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]

HSBP1 (HGNC:5203): (heat shock factor binding protein 1) The heat-shock response is elicited by exposure of cells to thermal and chemical stress and through the activation of HSFs (heat shock factors) results in the elevated expression of heat-shock induced genes. Heat shock factor binding protein 1 (HSBP1), is a 76-amino-acid protein that binds to heat shock factor 1(HSF1), which is a transcription factor involved in the HS response. During HS response, HSF1 undergoes conformational transition from an inert non-DNA-binding monomer to active functional trimers. HSBP1 is nuclear-localized and interacts with the active trimeric state of HSF1 to negatively regulate HSF1 DNA-binding activity. Overexpression of HSBP1 in mammalian cells represses the transactivation activity of HSF1. When overexpressed in C.elegans HSBP1 has severe effects on survival of the animals after thermal and chemical stress consistent with a role of HSBP1 as a negative regulator of heat shock response. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-83779906-G-A is Benign according to our data. Variant chr16-83779906-G-A is described in ClinVar as [Benign]. Clinvar id is 1277849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH13	NM_001257.5	c.1682-62G>A		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6	c.1682-62G>A		intron_variant		1	NM_001257.5	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38113 AN: 151802 Hom.: 5401 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.254 AC: 231768 AN: 911822 Hom.: 34322 AF XY: 0.256 AC XY: 118619 AN XY: 463164

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.655

Gnomad4 SAS exome AF: 0.332

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.251 AC: 38143 AN: 151918 Hom.: 5406 Cov.: 32 AF XY: 0.259 AC XY: 19256 AN XY: 74232

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.266

Alfa AF: 0.233 Hom.: 539

Bravo AF: 0.255

Asia WGS AF: 0.464 AC: 1612 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	-0.88
Cadd	Benign	0.0030
Dann	Benign	0.60

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: rs57930285; hg19: chr16-83813511; COSMIC: COSV51844168;