rs7216034

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.2046+22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,613,556 control chromosomes in the GnomAD database, including 445,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45311 hom., cov: 33)

Exomes 𝑓: 0.74 ( 400125 hom. )

Consequence

JUP
NM_002230.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.636

Publications

12 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=-0.89).

BP6

Variant 17-41757393-T-C is Benign according to our data. Variant chr17-41757393-T-C is described in ClinVar as Benign. ClinVar VariationId is 261475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 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.2046+22A>G	intron	N/A	NP_002221.1	P14923
JUP	NM_001352773.2		c.2046+22A>G	intron	N/A	NP_001339702.1	P14923
JUP	NM_001352774.2		c.2046+22A>G	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.2046+22A>G	intron	N/A	ENSP00000377508.3	P14923
JUP	ENST00000310706.9	TSL:1	c.2046+22A>G	intron	N/A	ENSP00000311113.5	P14923
JUP	ENST00000393930.5	TSL:5	c.2046+22A>G	intron	N/A	ENSP00000377507.1	P14923

Frequencies

GnomAD3 genomes

AF:

0.765

AC:

116390

AN:

152076

Hom.:

45258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.890

Gnomad AMI

AF:

0.876

Gnomad AMR

AF:

0.643

Gnomad ASJ

AF:

0.695

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.699

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.753

Gnomad OTH

AF:

0.738

GnomAD2 exomes

AF:

0.697

AC:

175270

AN:

251358

AF XY:

0.704

show subpopulations

Gnomad AFR exome

AF:

0.895

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.711

Gnomad EAS exome

AF:

0.502

Gnomad FIN exome

AF:

0.704

Gnomad NFE exome

AF:

0.745

Gnomad OTH exome

AF:

0.701

GnomAD4 exome

AF:

0.737

AC:

1077473

AN:

1461362

Hom.:

400125

Cov.:

AF XY:

0.737

AC XY:

536140

AN XY:

727006

show subpopulations

African (AFR)

AF:

0.896

AC:

29990

AN:

33474

American (AMR)

AF:

0.534

AC:

23872

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.708

AC:

18490

AN:

26134

East Asian (EAS)

AF:

0.525

AC:

20839

AN:

39696

South Asian (SAS)

AF:

0.725

AC:

62531

AN:

86222

European-Finnish (FIN)

AF:

0.707

AC:

37675

AN:

53322

Middle Eastern (MID)

AF:

0.729

AC:

4205

AN:

5766

European-Non Finnish (NFE)

AF:

0.752

AC:

835701

AN:

1111652

Other (OTH)

AF:

0.732

AC:

44170

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

15789

31577

47366

63154

78943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20218

40436

60654

80872

101090

<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:

0.765

AC:

116498

AN:

152194

Hom.:

45311

Cov.:

AF XY:

0.760

AC XY:

56506

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.890

AC:

37004

AN:

41560

American (AMR)

AF:

0.643

AC:

9815

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.695

AC:

2412

AN:

3470

East Asian (EAS)

AF:

0.512

AC:

2645

AN:

5170

South Asian (SAS)

AF:

0.715

AC:

3452

AN:

4826

European-Finnish (FIN)

AF:

0.699

AC:

7392

AN:

10582

Middle Eastern (MID)

AF:

0.748

AC:

220

AN:

294

European-Non Finnish (NFE)

AF:

0.753

AC:

51192

AN:

67990

Other (OTH)

AF:

0.741

AC:

1569

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1387

2774

4160

5547

6934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.766

Hom.:

9697

Bravo

AF:

0.763

Asia WGS

AF:

0.640

AC:

2225

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Arrhythmogenic right ventricular dysplasia 12 (1)

Naxos disease (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.33

PhyloP100

-0.64

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