Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002230.4(JUP):c.213T>C(p.Asp71Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,606,858 control chromosomes in the GnomAD database, including 458,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45851 hom., cov: 32)

Exomes 𝑓: 0.75 ( 412516 hom. )

Consequence

JUP
NM_002230.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:17

Conservation

PhyloP100: 0.455

Publications

22 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 17-41769673-A-G is Benign according to our data. Variant chr17-41769673-A-G is described in ClinVar as Benign. ClinVar VariationId is 45845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.455 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 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	HGVSp	Effect	Exon Rank	Protein
JUP	NM_002230.4	MANE Select	c.213T>C	p.Asp71Asp	synonymous	Exon 3 of 14	NP_002221.1
JUP	NM_001352773.2		c.213T>C	p.Asp71Asp	synonymous	Exon 3 of 14	NP_001339702.1
JUP	NM_001352774.2		c.213T>C	p.Asp71Asp	synonymous	Exon 3 of 15	NP_001339703.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
JUP	ENST00000393931.8	TSL:1 MANE Select	c.213T>C	p.Asp71Asp	synonymous	Exon 3 of 14	ENSP00000377508.3
JUP	ENST00000310706.9	TSL:1	c.213T>C	p.Asp71Asp	synonymous	Exon 3 of 15	ENSP00000311113.5
JUP	ENST00000393930.5	TSL:5	c.213T>C	p.Asp71Asp	synonymous	Exon 3 of 15	ENSP00000377507.1

Frequencies

GnomAD3 genomes

AF:

0.771

AC:

117207

AN:

152052

Hom.:

45801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.882

Gnomad AMI

AF:

0.752

Gnomad AMR

AF:

0.658

Gnomad ASJ

AF:

0.809

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.748

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.829

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.763

GnomAD2 exomes

AF:

0.711

AC:

167306

AN:

235266

AF XY:

0.721

show subpopulations

Gnomad AFR exome

AF:

0.887

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.826

Gnomad EAS exome

AF:

0.511

Gnomad FIN exome

AF:

0.681

Gnomad NFE exome

AF:

0.758

Gnomad OTH exome

AF:

0.734

GnomAD4 exome

AF:

0.750

AC:

1091432

AN:

1454688

Hom.:

412516

Cov.:

AF XY:

0.752

AC XY:

543348

AN XY:

722944

show subpopulations

African (AFR)

AF:

0.890

AC:

29779

AN:

33464

American (AMR)

AF:

0.538

AC:

23402

AN:

43516

Ashkenazi Jewish (ASJ)

AF:

0.816

AC:

21059

AN:

25804

East Asian (EAS)

AF:

0.518

AC:

20448

AN:

39484

South Asian (SAS)

AF:

0.759

AC:

64248

AN:

84700

European-Finnish (FIN)

AF:

0.684

AC:

35616

AN:

52044

Middle Eastern (MID)

AF:

0.805

AC:

4590

AN:

5700

European-Non Finnish (NFE)

AF:

0.763

AC:

846722

AN:

1109814

Other (OTH)

AF:

0.757

AC:

45568

AN:

60162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

15408

30815

46223

61630

77038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20336

40672

61008

81344

101680

<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:

0.771

AC:

117318

AN:

152170

Hom.:

45851

Cov.:

AF XY:

0.762

AC XY:

56711

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.882

AC:

36641

AN:

41536

American (AMR)

AF:

0.657

AC:

10050

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.809

AC:

2807

AN:

3468

East Asian (EAS)

AF:

0.517

AC:

2664

AN:

5150

South Asian (SAS)

AF:

0.750

AC:

3620

AN:

4828

European-Finnish (FIN)

AF:

0.670

AC:

7085

AN:

10582

Middle Eastern (MID)

AF:

0.820

AC:

241

AN:

294

European-Non Finnish (NFE)

AF:

0.763

AC:

51904

AN:

68000

Other (OTH)

AF:

0.767

AC:

1620

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1377

2754

4131

5508

6885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<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:

0.754

Hom.:

27783

Bravo

AF:

0.770

Asia WGS

AF:

0.673

AC:

2346

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (8)

Arrhythmogenic right ventricular dysplasia 12 (2)

Naxos disease (2)

not provided (2)

Cardiomyopathy (1)

Cardiovascular phenotype (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.5

(source)

DANN

Benign

0.52

PhyloP100

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=94/6

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.

rs7405731

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over