4-75771745-C-T

Variant names:

• chr4-75771745-C-T
• rs226416
• NM_003715.4:c.555+608C>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.555+608C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,296 control chromosomes in the GnomAD database, including 62,372 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 0.90 (62372 hom., cov: 34)
• Consequence: USO1 NM_003715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.97 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.555+608C>T		intron	N/A	NP_003706.2
	USO1	NM_001290049.2		c.567+608C>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.555+608C>T		intron	N/A	ENSP00000444850.2
	USO1	ENST00000264904.8	TSL:2	c.567+608C>T		intron	N/A	ENSP00000264904.7

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137534 AN: 152178 Hom.: 62313 Cov.: 34

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.904 AC: 137653 AN: 152296 Hom.: 62372 Cov.: 34 AF XY: 0.903 AC XY: 67235 AN XY: 74466

African (AFR) AF: 0.978 AC: 40647 AN: 41578

American (AMR) AF: 0.885 AC: 13546 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3022 AN: 3472

East Asian (EAS) AF: 0.906 AC: 4704 AN: 5190

South Asian (SAS) AF: 0.895 AC: 4323 AN: 4830

European-Finnish (FIN) AF: 0.873 AC: 9239 AN: 10586

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.871 AC: 59247 AN: 68020

Other (OTH) AF: 0.883 AC: 1868 AN: 2116

Alfa AF: 0.878 Hom.: 71185

Bravo AF: 0.907

Asia WGS AF: 0.906 AC: 3147 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs226416; hg19: chr4-76692898;