rs73983658

Variant names:

Variant summary

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

The NM_002230.4(JUP):c.1653+10C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00839 in 1,598,466 control chromosomes in the GnomAD database, including 934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 455 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 479 hom. )

Consequence

JUP
NM_002230.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.735

Publications

3 publications found

Variant links:

Genes affected

JUP (HGNC:6207): (junction plakoglobin) This gene encodes a major cytoplasmic protein which is the only known constituent common to submembranous plaques of both desmosomes and intermediate junctions. This protein forms distinct complexes with cadherins and desmosomal cadherins and is a member of the catenin family since it contains a distinct repeating amino acid motif called the armadillo repeat. Mutation in this gene has been associated with Naxos disease. Alternative splicing occurs in this gene; however, not all transcripts have been fully described. [provided by RefSeq, Jul 2008]

JUP Gene-Disease associations (from GenCC):

arrhythmogenic right ventricular dysplasia 12
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
inherited epidermolysis bullosa
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
Naxos disease
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)
lethal acantholytic epidermolysis bullosa
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

JUP links:

Genome browser will be placed here

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=-0.79).

BP6

Variant 17-41758705-G-T is Benign according to our data. Variant chr17-41758705-G-T is described in ClinVar as Benign. ClinVar VariationId is 45838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JUP	NM_002230.4 link	c.1653+10C>A		intron_variant	Intron 9 of 13	ENST00000393931.8	NP_002221.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
JUP	ENST00000393931.8 link	c.1653+10C>A	intron_variant	Intron 9 of 13	1	NM_002230.4	ENSP00000377508.3
JUP	ENST00000310706.9 link	c.1653+10C>A	intron_variant	Intron 9 of 14	1		ENSP00000311113.5
JUP	ENST00000393930.5 link	c.1653+10C>A	intron_variant	Intron 9 of 14	5		ENSP00000377507.1
JUP	ENST00000585793.1 link	n.251+10C>A	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0427

AC:

6501

AN:

152138

Hom.:

446

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0161

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.0301

GnomAD2 exomes

AF:

0.0111

AC:

2456

AN:

222132

AF XY:

0.00813

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.00590

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000181

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000434

Gnomad OTH exome

AF:

0.00683

GnomAD4 exome

AF:

0.00475

AC:

6865

AN:

1446210

Hom.:

479

Cov.:

AF XY:

0.00415

AC XY:

2983

AN XY:

718304

show subpopulations

African (AFR)

AF:

0.160

AC:

5303

AN:

33042

American (AMR)

AF:

0.00786

AC:

334

AN:

42484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25794

East Asian (EAS)

AF:

0.000129

AC:

AN:

38748

South Asian (SAS)

AF:

0.00185

AC:

156

AN:

84128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51462

Middle Eastern (MID)

AF:

0.0112

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.000222

AC:

245

AN:

1105018

Other (OTH)

AF:

0.0127

AC:

758

AN:

59816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

331

662

994

1325

1656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

344

516

688

860

<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:

0.0430

AC:

6540

AN:

152256

Hom.:

455

Cov.:

AF XY:

0.0411

AC XY:

3057

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.149

AC:

6174

AN:

41520

American (AMR)

AF:

0.0161

AC:

246

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00269

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68018

Other (OTH)

AF:

0.0350

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

280

560

840

1120

1400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0394

Hom.:

117

Bravo

AF:

0.0489

Asia WGS

AF:

0.0480

AC:

166

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 24, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Naxos disease

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Cardiomyopathy

Benign:1

Sep 23, 2022

Cohesion Phenomics

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Arrhythmogenic right ventricular dysplasia 12

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Naxos disease;C1969081:Arrhythmogenic right ventricular dysplasia 12

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

0.73

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over