rs6845147

Positions:

• chr4-75803940-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003715.4(USO1):​c.1987-194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,898 control chromosomes in the GnomAD database, including 23,440 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 0.53 (23440 hom., cov: 31)
• Consequence: USO1 NM_003715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USO1	NM_003715.4	c.1987-194G>A		intron_variant		ENST00000514213.7	NP_003706.2
USO1	NM_001290049.2	c.2020-194G>A		intron_variant			NP_001276978.1
USO1	XM_006714396.5	c.2008-194G>A		intron_variant			XP_006714459.1
USO1	XM_006714397.4	c.1999-194G>A		intron_variant			XP_006714460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USO1	ENST00000514213.7	c.1987-194G>A		intron_variant		1	NM_003715.4	ENSP00000444850.2
USO1	ENST00000264904.8	c.2020-194G>A		intron_variant		2		ENSP00000264904.7

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81175 AN: 151780 Hom.: 23440 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.535 AC: 81196 AN: 151898 Hom.: 23440 Cov.: 31 AF XY: 0.537 AC XY: 39874 AN XY: 74240

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.558

Alfa AF: 0.590 Hom.: 5529

Bravo AF: 0.525

Asia WGS AF: 0.659 AC: 2289 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.40

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: rs6845147; hg19: chr4-76725093;