chr4-75785543-C-T

Variant names:

• chr4-75785543-C-T
• rs324734
• NM_003715.4:c.856-1519C>T

Variant summary

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

The NM_003715.4(USO1):​c.856-1519C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 151,908 control chromosomes in the GnomAD database, including 49,103 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 0.80 (49103 hom., cov: 30)
• Consequence: USO1 NM_003715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 3 publications found

Genes affected

USO1 (HGNC:30904): (USO1 vesicle transport factor) The protein encoded by this gene is a peripheral membrane protein which recycles between the cytosol and the Golgi apparatus during interphase. It is regulated by phosphorylation: dephosphorylated protein associates with the Golgi membrane and dissociates from the membrane upon phosphorylation. Ras-associated protein 1 recruits this protein to coat protein complex II (COPII) vesicles during budding from the endoplasmic reticulum, where it interacts with a set of COPII vesicle-associated SNAREs to form a cis-SNARE complex that promotes targeting to the Golgi apparatus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003715.4. 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
	USO1	NM_003715.4	MANE Select	c.856-1519C>T		intron	N/A	NP_003706.2	O60763-1
	USO1	NM_001290049.2		c.868-1519C>T		intron	N/A	NP_001276978.1	O60763-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USO1	ENST00000514213.7	TSL:1 MANE Select	c.856-1519C>T		intron	N/A	ENSP00000444850.2	O60763-1
	USO1	ENST00000264904.8	TSL:2	c.868-1519C>T		intron	N/A	ENSP00000264904.7	O60763-2
	USO1	ENST00000944458.1		c.868-1519C>T		intron	N/A	ENSP00000614517.1

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121802 AN: 151790 Hom.: 49054 Cov.: 30

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.803 AC: 121908 AN: 151908 Hom.: 49103 Cov.: 30 AF XY: 0.806 AC XY: 59839 AN XY: 74248

African (AFR) AF: 0.758 AC: 31425 AN: 41444

American (AMR) AF: 0.849 AC: 12946 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2955 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5136 AN: 5168

South Asian (SAS) AF: 0.872 AC: 4194 AN: 4812

European-Finnish (FIN) AF: 0.816 AC: 8606 AN: 10544

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 53961 AN: 67908

Other (OTH) AF: 0.820 AC: 1728 AN: 2108

Alfa AF: 0.803 Hom.: 8307

Bravo AF: 0.801

Asia WGS AF: 0.909 AC: 3121 AN: 3434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.16
PhyloP100		0.42
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: rs324734; hg19: chr4-76706696;