16-83783016-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001257.5(CDH13):​c.1916-238T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 152,170 control chromosomes in the GnomAD database, including 56,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.86 ( 56134 hom., cov: 32)

Consequence

CDH13
NM_001257.5 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.902
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BP6
Variant 16-83783016-T-C is Benign according to our data. Variant chr16-83783016-T-C is described in ClinVar as [Benign]. Clinvar id is 1274750.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDH13NM_001257.5 linkuse as main transcriptc.1916-238T>C intron_variant ENST00000567109.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDH13ENST00000567109.6 linkuse as main transcriptc.1916-238T>C intron_variant 1 NM_001257.5 P1P55290-1

Frequencies

GnomAD3 genomes
AF:
0.859
AC:
130592
AN:
152052
Hom.:
56094
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.863
Gnomad AMI
AF:
0.823
Gnomad AMR
AF:
0.879
Gnomad ASJ
AF:
0.855
Gnomad EAS
AF:
0.800
Gnomad SAS
AF:
0.863
Gnomad FIN
AF:
0.832
Gnomad MID
AF:
0.813
Gnomad NFE
AF:
0.861
Gnomad OTH
AF:
0.871
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.859
AC:
130685
AN:
152170
Hom.:
56134
Cov.:
32
AF XY:
0.857
AC XY:
63772
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.863
Gnomad4 AMR
AF:
0.879
Gnomad4 ASJ
AF:
0.855
Gnomad4 EAS
AF:
0.800
Gnomad4 SAS
AF:
0.864
Gnomad4 FIN
AF:
0.832
Gnomad4 NFE
AF:
0.861
Gnomad4 OTH
AF:
0.864
Alfa
AF:
0.858
Hom.:
6950
Bravo
AF:
0.863
Asia WGS
AF:
0.837
AC:
2912
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 18, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.57
DANN
Benign
0.53

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.

Other links and lift over

dbSNP: rs153653; hg19: chr16-83816621; API