4-75783861-A-T

Variant names:

• chr4-75783861-A-T
• rs324735
• NM_003715.4:c.855+1003A>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.855+1003A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,092 control chromosomes in the GnomAD database, including 34,077 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 0.65 (34077 hom., cov: 32)
• Consequence: USO1 NM_003715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USO1	NM_003715.4	MANE Select	c.855+1003A>T		intron	N/A	NP_003706.2
	USO1	NM_001290049.2		c.867+1003A>T		intron	N/A	NP_001276978.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USO1	ENST00000514213.7	TSL:1 MANE Select	c.855+1003A>T		intron	N/A	ENSP00000444850.2
	USO1	ENST00000264904.8	TSL:2	c.867+1003A>T		intron	N/A	ENSP00000264904.7

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98443 AN: 151974 Hom.: 34065 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.648 AC: 98500 AN: 152092 Hom.: 34077 Cov.: 32 AF XY: 0.650 AC XY: 48363 AN XY: 74352

African (AFR) AF: 0.383 AC: 15862 AN: 41464

American (AMR) AF: 0.729 AC: 11132 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2847 AN: 3470

East Asian (EAS) AF: 0.908 AC: 4702 AN: 5178

South Asian (SAS) AF: 0.667 AC: 3218 AN: 4826

European-Finnish (FIN) AF: 0.757 AC: 8012 AN: 10586

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50396 AN: 67976

Other (OTH) AF: 0.685 AC: 1447 AN: 2112

Alfa AF: 0.689 Hom.: 4659

Bravo AF: 0.635

Asia WGS AF: 0.763 AC: 2650 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.1
DANN	Benign	0.46
PhyloP100		0.12
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: rs324735; hg19: chr4-76705014;