Variant chr16-83779906-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.48

Variant links:

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 links:

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]

HSBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 linkuse as main transcript	c.1682-62G>A		intron_variant		ENST00000567109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH13	ENST00000567109.6 linkuse as main transcript	c.1682-62G>A		intron_variant		1	NM_001257.5	P1	P55290-1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38113

AN:

151802

Hom.:

5401

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.259

AC XY:

19256

AN XY:

74232

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over