rs12942034

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.909+17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,611,860 control chromosomes in the GnomAD database, including 522,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 50207 hom., cov: 32)

Exomes 𝑓: 0.80 ( 472130 hom. )

Consequence

JUP
NM_002230.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.00800

Publications

9 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=-0.96).

BP6

Variant 17-41767362-A-G is Benign according to our data. Variant chr17-41767362-A-G is described in ClinVar as Benign. ClinVar VariationId is 258593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 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.909+17T>C	intron	N/A	NP_002221.1	P14923
JUP	NM_001352773.2		c.909+17T>C	intron	N/A	NP_001339702.1	P14923
JUP	NM_001352774.2		c.909+17T>C	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.909+17T>C	intron	N/A	ENSP00000377508.3	P14923
JUP	ENST00000310706.9	TSL:1	c.909+17T>C	intron	N/A	ENSP00000311113.5	P14923
JUP	ENST00000393930.5	TSL:5	c.909+17T>C	intron	N/A	ENSP00000377507.1	P14923

Frequencies

GnomAD3 genomes

AF:

0.808

AC:

122885

AN:

152080

Hom.:

50160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.886

Gnomad AMI

AF:

0.803

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.789

Gnomad EAS

AF:

0.510

Gnomad SAS

AF:

0.790

Gnomad FIN

AF:

0.785

Gnomad MID

AF:

0.820

Gnomad NFE

AF:

0.818

Gnomad OTH

AF:

0.798

GnomAD2 exomes

AF:

0.751

AC:

188199

AN:

250442

AF XY:

0.763

show subpopulations

Gnomad AFR exome

AF:

0.892

Gnomad AMR exome

AF:

0.531

Gnomad ASJ exome

AF:

0.803

Gnomad EAS exome

AF:

0.501

Gnomad FIN exome

AF:

0.787

Gnomad NFE exome

AF:

0.814

Gnomad OTH exome

AF:

0.768

GnomAD4 exome

AF:

0.801

AC:

1169037

AN:

1459662

Hom.:

472130

Cov.:

AF XY:

0.802

AC XY:

582409

AN XY:

726206

show subpopulations

African (AFR)

AF:

0.890

AC:

29764

AN:

33440

American (AMR)

AF:

0.548

AC:

24500

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.797

AC:

20829

AN:

26120

East Asian (EAS)

AF:

0.509

AC:

20216

AN:

39688

South Asian (SAS)

AF:

0.800

AC:

68945

AN:

86206

European-Finnish (FIN)

AF:

0.788

AC:

41812

AN:

53080

Middle Eastern (MID)

AF:

0.809

AC:

4586

AN:

5668

European-Non Finnish (NFE)

AF:

0.820

AC:

910565

AN:

1110484

Other (OTH)

AF:

0.793

AC:

47820

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

12695

25390

38085

50780

63475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20798

41596

62394

83192

103990

<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:

0.808

AC:

122992

AN:

152198

Hom.:

50207

Cov.:

AF XY:

0.801

AC XY:

59600

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.886

AC:

36833

AN:

41560

American (AMR)

AF:

0.677

AC:

10352

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.789

AC:

2738

AN:

3470

East Asian (EAS)

AF:

0.510

AC:

2629

AN:

5156

South Asian (SAS)

AF:

0.792

AC:

3818

AN:

4822

European-Finnish (FIN)

AF:

0.785

AC:

8304

AN:

10580

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.818

AC:

55659

AN:

68010

Other (OTH)

AF:

0.798

AC:

1688

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1180

2361

3541

4722

5902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<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:

0.815

Hom.:

9313

Bravo

AF:

0.798

Asia WGS

AF:

0.683

AC:

2379

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Arrhythmogenic right ventricular dysplasia 12 (1)

Cardiomyopathy (1)

Naxos disease (1)

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

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.0

(source)

DANN

Benign

0.74

PhyloP100

-0.0080

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