chr16-83747999-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001257.5(CDH13):c.1539-109T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,152,732 control chromosomes in the GnomAD database, including 79,216 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10035 hom., cov: 30)

Exomes 𝑓: 0.37 ( 69181 hom. )

Consequence

CDH13
NM_001257.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0220

Publications

9 publications found

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:

CEDORA (HGNC:56653): (CDH13 antisense oligodendrocyte and neuron associated lncRNA)

CEDORA 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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-83747999-T-C is Benign according to our data. Variant chr16-83747999-T-C is described in ClinVar as Benign. ClinVar VariationId is 1241198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDH13	NM_001257.5	MANE Select	c.1539-109T>C	intron	N/A	NP_001248.1	P55290-1
CDH13	NM_001220488.2		c.1680-109T>C	intron	N/A	NP_001207417.1	P55290-4
CDH13	NM_001220489.2		c.1422-109T>C	intron	N/A	NP_001207418.1	P55290-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDH13	ENST00000567109.6	TSL:1 MANE Select	c.1539-109T>C	intron	N/A	ENSP00000479395.1	P55290-1
CDH13	ENST00000268613.14	TSL:2	c.1680-109T>C	intron	N/A	ENSP00000268613.10	P55290-4
CDH13	ENST00000428848.7	TSL:2	c.1422-109T>C	intron	N/A	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55046

AN:

151692

Hom.:

10030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.411

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.362

GnomAD4 exome

AF:

0.368

AC:

368375

AN:

1000922

Hom.:

69181

AF XY:

0.368

AC XY:

188072

AN XY:

511602

show subpopulations

African (AFR)

AF:

0.337

AC:

8143

AN:

24176

American (AMR)

AF:

0.395

AC:

15316

AN:

38728

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

6750

AN:

20722

East Asian (EAS)

AF:

0.440

AC:

16403

AN:

37308

South Asian (SAS)

AF:

0.357

AC:

24846

AN:

69630

European-Finnish (FIN)

AF:

0.401

AC:

19513

AN:

48618

Middle Eastern (MID)

AF:

0.428

AC:

1983

AN:

4638

European-Non Finnish (NFE)

AF:

0.364

AC:

259106

AN:

712442

Other (OTH)

AF:

0.365

AC:

16315

AN:

44660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

11395

22790

34184

45579

56974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6942

13884

20826

27768

34710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.363

AC:

55086

AN:

151810

Hom.:

10035

Cov.:

AF XY:

0.363

AC XY:

26905

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.329

AC:

13599

AN:

41378

American (AMR)

AF:

0.383

AC:

5840

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

1145

AN:

3468

East Asian (EAS)

AF:

0.421

AC:

2171

AN:

5162

South Asian (SAS)

AF:

0.366

AC:

1760

AN:

4806

European-Finnish (FIN)

AF:

0.411

AC:

4327

AN:

10532

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.368

AC:

25023

AN:

67914

Other (OTH)

AF:

0.363

AC:

763

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1802

3604

5405

7207

9009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.362

Hom.:

4462

Bravo

AF:

0.362

Asia WGS

AF:

0.419

AC:

1462

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

(source)

DANN

Benign

0.53

PhyloP100

0.022

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over