16-83794939-C-G

Position:

• chr16-83794939-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001257.5(CDH13):​c.2135-84C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,243,196 control chromosomes in the GnomAD database, including 37,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4249 hom., cov: 32)
  • Exomes 𝑓: 0.22 (33123 hom.)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0630

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]

CDH13-AS2 (HGNC:56243): (CDH13 antisense RNA 2)

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-83794939-C-G is Benign according to our data. Variant chr16-83794939-C-G is described in ClinVar as [Benign]. Clinvar id is 1239166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH13	NM_001257.5	c.2135-84C>G		intron_variant		ENST00000567109.6	NP_001248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH13	ENST00000567109.6	c.2135-84C>G		intron_variant		1	NM_001257.5	ENSP00000479395	P1
CDH13-AS2	ENST00000565714.5	n.95-4735G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31321 AN: 151870 Hom.: 4250 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.221 AC: 241567 AN: 1091208 Hom.: 33123 AF XY: 0.224 AC XY: 123925 AN XY: 552882

Gnomad4 AFR exome AF: 0.0945

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.660

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.185

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.206 AC: 31326 AN: 151988 Hom.: 4249 Cov.: 32 AF XY: 0.217 AC XY: 16095 AN XY: 74262

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.234

Alfa AF: 0.184 Hom.: 395

Bravo AF: 0.211

Asia WGS AF: 0.444 AC: 1544 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.34

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: rs3743617; hg19: chr16-83828544;