Genetic Variant CDH13:c.1682-151C>T (chr16-83779817-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001257.5(CDH13):c.1682-151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 582,746 control chromosomes in the GnomAD database, including 369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 93 hom., cov: 32)

Exomes 𝑓: 0.031 ( 276 hom. )

Consequence

CDH13
NM_001257.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.07

Publications

0 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:

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=-0.89).

BP6

Variant 16-83779817-C-T is Benign according to our data. Variant chr16-83779817-C-T is described in ClinVar as Benign. ClinVar VariationId is 1237494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0269 (4095/152248) while in subpopulation NFE AF = 0.0381 (2593/68016). AF 95% confidence interval is 0.0369. There are 93 homozygotes in GnomAd4. There are 2041 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 93 gene

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.1682-151C>T	intron	N/A	NP_001248.1	P55290-1
CDH13	NM_001220488.2		c.1823-151C>T	intron	N/A	NP_001207417.1	P55290-4
CDH13	NM_001220489.2		c.1565-151C>T	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.1682-151C>T	intron	N/A	ENSP00000479395.1	P55290-1
CDH13	ENST00000268613.14	TSL:2	c.1823-151C>T	intron	N/A	ENSP00000268613.10	P55290-4
CDH13	ENST00000428848.7	TSL:2	c.1565-151C>T	intron	N/A	ENSP00000394557.3	P55290-5

Frequencies

GnomAD3 genomes

AF:

0.0269

AC:

4094

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00679

Gnomad AMI

AF:

0.0989

Gnomad AMR

AF:

0.0225

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0603

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0381

Gnomad OTH

AF:

0.0225

GnomAD4 exome

AF:

0.0307

AC:

13209

AN:

430498

Hom.:

276

AF XY:

0.0301

AC XY:

6731

AN XY:

223958

show subpopulations

African (AFR)

AF:

0.00707

AC:

AN:

12306

American (AMR)

AF:

0.0188

AC:

331

AN:

17568

Ashkenazi Jewish (ASJ)

AF:

0.00775

AC:

101

AN:

13034

East Asian (EAS)

AF:

0.000197

AC:

AN:

30528

South Asian (SAS)

AF:

0.0146

AC:

526

AN:

35922

European-Finnish (FIN)

AF:

0.0590

AC:

1711

AN:

29012

Middle Eastern (MID)

AF:

0.0307

AC:

102

AN:

3322

European-Non Finnish (NFE)

AF:

0.0364

AC:

9599

AN:

263716

Other (OTH)

AF:

0.0297

AC:

746

AN:

25090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

606

1212

1819

2425

3031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<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:

0.0269

AC:

4095

AN:

152248

Hom.:

Cov.:

AF XY:

0.0274

AC XY:

2041

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00677

AC:

281

AN:

41536

American (AMR)

AF:

0.0225

AC:

344

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.0151

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0603

AC:

639

AN:

10594

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0381

AC:

2593

AN:

68016

Other (OTH)

AF:

0.0222

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

210

420

630

840

1050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0109

Hom.:

Bravo

AF:

0.0231

Asia WGS

AF:

0.0110

AC:

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

-0.89

CADD

Benign

1.7

(source)

DANN

Benign

0.65

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism

(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