rs4820345

Positions:

• chr22-38695146-T-C
• chr22-38695146-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JOSD1	NM_001360236.2	c.185+4657A>G		intron_variant		ENST00000683374.1	NP_001347165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JOSD1	ENST00000683374.1	c.185+4657A>G		intron_variant			NM_001360236.2	ENSP00000506752.1

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

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.260

Alfa AF: 0.266 Hom.: 5172

Bravo AF: 0.237

Asia WGS AF: 0.311 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.77
DANN	Benign	0.53

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

LitVar

Other links and lift over

dbSNP: rs4820345; hg19: chr22-39091151;