Genetic Variant JOSD1:c.185+110G>C (chr22-38699693-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001360236.2(JOSD1):c.185+110G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,030,820 control chromosomes in the GnomAD database, including 56,946 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 11116 hom., cov: 32)

Exomes 𝑓: 0.32 ( 45830 hom. )

Consequence

JOSD1
NM_001360236.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.260

Publications

14 publications found

Variant links:

Genes affected

JOSD1 (HGNC:28953): (Josephin domain containing 1) Predicted to enable thiol-dependent deubiquitinase. Predicted to be involved in protein deubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

JOSD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001360236.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
JOSD1	NM_001360236.2	MANE Select	c.185+110G>C	intron	N/A	NP_001347165.1
JOSD1	NM_001360235.2		c.185+110G>C	intron	N/A	NP_001347164.1
JOSD1	NM_014876.7		c.185+110G>C	intron	N/A	NP_055691.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
JOSD1	ENST00000683374.1	MANE Select	c.185+110G>C	intron	N/A	ENSP00000506752.1
JOSD1	ENST00000216039.9	TSL:1	c.185+110G>C	intron	N/A	ENSP00000216039.5
JOSD1	ENST00000545590.1	TSL:3	c.167+110G>C	intron	N/A	ENSP00000444798.1

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56341

AN:

151936

Hom.:

11099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.338

GnomAD4 exome

AF:

0.316

AC:

277934

AN:

878766

Hom.:

45830

AF XY:

0.315

AC XY:

144172

AN XY:

457954

show subpopulations

African (AFR)

AF:

0.508

AC:

10733

AN:

21146

American (AMR)

AF:

0.231

AC:

8496

AN:

36702

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

6325

AN:

20512

East Asian (EAS)

AF:

0.491

AC:

18105

AN:

36886

South Asian (SAS)

AF:

0.289

AC:

20273

AN:

70034

European-Finnish (FIN)

AF:

0.341

AC:

17509

AN:

51372

Middle Eastern (MID)

AF:

0.332

AC:

980

AN:

2954

European-Non Finnish (NFE)

AF:

0.305

AC:

182353

AN:

598270

Other (OTH)

AF:

0.322

AC:

13160

AN:

40890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

9443

18886

28329

37772

47215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4230

8460

12690

16920

21150

<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:

0.371

AC:

56404

AN:

152054

Hom.:

11116

Cov.:

AF XY:

0.369

AC XY:

27409

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.505

AC:

20946

AN:

41460

American (AMR)

AF:

0.266

AC:

4065

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.311

AC:

1080

AN:

3472

East Asian (EAS)

AF:

0.463

AC:

2394

AN:

5172

South Asian (SAS)

AF:

0.311

AC:

1503

AN:

4826

European-Finnish (FIN)

AF:

0.337

AC:

3560

AN:

10576

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.319

AC:

21655

AN:

67950

Other (OTH)

AF:

0.343

AC:

724

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1753

3507

5260

7014

8767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.347

Hom.:

1230

Bravo

AF:

0.371

Asia WGS

AF:

0.391

AC:

1362

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.4

(source)

DANN

Benign

0.54

PhyloP100

-0.26

PromoterAI

-0.041

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over