rs116772523

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1774-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00397 in 1,600,546 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 100 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 114 hom. )

Consequence

JUP
NM_002230.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.389

Publications

1 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 cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
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, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet
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=-0.83).

BP6

Variant 17-41757797-G-A is Benign according to our data. Variant chr17-41757797-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 36424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002230.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
JUP	NM_002230.4	MANE Select	c.1774-13C>T	intron	N/A	NP_002221.1	P14923
JUP	NM_001352773.2		c.1774-13C>T	intron	N/A	NP_001339702.1	P14923
JUP	NM_001352774.2		c.1774-13C>T	intron	N/A	NP_001339703.1	P14923

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
JUP	ENST00000393931.8	TSL:1 MANE Select	c.1774-13C>T	intron	N/A	ENSP00000377508.3	P14923
JUP	ENST00000310706.9	TSL:1	c.1774-13C>T	intron	N/A	ENSP00000311113.5	P14923
JUP	ENST00000393930.5	TSL:5	c.1774-13C>T	intron	N/A	ENSP00000377507.1	P14923

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3292

AN:

152152

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0758

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0173

GnomAD2 exomes

AF:

0.00553

AC:

1293

AN:

233794

AF XY:

0.00406

show subpopulations

Gnomad AFR exome

AF:

0.0744

Gnomad AMR exome

AF:

0.00354

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000864

Gnomad OTH exome

AF:

0.00297

GnomAD4 exome

AF:

0.00212

AC:

3066

AN:

1448276

Hom.:

114

Cov.:

AF XY:

0.00183

AC XY:

1317

AN XY:

719100

show subpopulations

African (AFR)

AF:

0.0772

AC:

2563

AN:

33210

American (AMR)

AF:

0.00368

AC:

161

AN:

43736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25162

East Asian (EAS)

AF:

0.00

AC:

AN:

39546

South Asian (SAS)

AF:

0.0000595

AC:

AN:

83994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52728

Middle Eastern (MID)

AF:

0.00253

AC:

AN:

5146

European-Non Finnish (NFE)

AF:

0.0000480

AC:

AN:

1105032

Other (OTH)

AF:

0.00454

AC:

271

AN:

59722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

140

280

420

560

700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.0216

AC:

3293

AN:

152270

Hom.:

100

Cov.:

AF XY:

0.0208

AC XY:

1545

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0756

AC:

3139

AN:

41540

American (AMR)

AF:

0.00693

AC:

106

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

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:

0.000162

AC:

AN:

68034

Other (OTH)

AF:

0.0171

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

163

325

488

650

813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00479

Hom.:

Bravo

AF:

0.0248

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

not provided (2)

Arrhythmogenic right ventricular dysplasia 12 (1)

Cardiac arrhythmia (1)

Cardiomyopathy (1)

Naxos disease (1)

Naxos disease;C1969081:Arrhythmogenic right ventricular dysplasia 12 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.065

(source)

DANN

Benign

0.82

PhyloP100

0.39

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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