NM_001360236.2:c.185+4657A>G

Variant names:

• chr22-38695146-T-C
• rs4820345
• NM_001360236.2:c.185+4657A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001360236.2(JOSD1):​c.185+4657A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,116 control chromosomes in the GnomAD database, including 5,278 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 0.25 (5278 hom., cov: 32)
• Consequence: JOSD1 NM_001360236.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 9 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JOSD1	NM_001360236.2	MANE Select	c.185+4657A>G		intron	N/A	NP_001347165.1	Q15040
	JOSD1	NM_001360235.2		c.185+4657A>G		intron	N/A	NP_001347164.1	Q15040
	JOSD1	NM_014876.7		c.185+4657A>G		intron	N/A	NP_055691.1	Q15040

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JOSD1	ENST00000683374.1	MANE Select	c.185+4657A>G		intron	N/A	ENSP00000506752.1	Q15040
	JOSD1	ENST00000216039.9	TSL:1	c.185+4657A>G		intron	N/A	ENSP00000216039.5	Q15040
	JOSD1	ENST00000866135.1		c.185+4657A>G		intron	N/A	ENSP00000536194.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38371 AN: 151996 Hom.: 5274 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.252 AC: 38392 AN: 152116 Hom.: 5278 Cov.: 32 AF XY: 0.254 AC XY: 18905 AN XY: 74364

African (AFR) AF: 0.145 AC: 6033 AN: 41508

American (AMR) AF: 0.223 AC: 3413 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1000 AN: 3470

East Asian (EAS) AF: 0.359 AC: 1860 AN: 5176

South Asian (SAS) AF: 0.276 AC: 1332 AN: 4824

European-Finnish (FIN) AF: 0.334 AC: 3523 AN: 10554

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20221 AN: 67980

Other (OTH) AF: 0.260 AC: 550 AN: 2116

Alfa AF: 0.262 Hom.: 6690

Bravo AF: 0.237

Asia WGS AF: 0.311 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.77
DANN	Benign	0.53
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4820345; hg19: chr22-39091151;