Variant 3-33402794-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014517.5(UBP1):c.1031+7A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,545,238 control chromosomes in the GnomAD database, including 363,820 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.62 ( 29895 hom., cov: 31)

Exomes 𝑓: 0.69 ( 333925 hom. )

Consequence

UBP1
NM_014517.5 splice_region, intron

Scores

Splicing: ADA: 0.00002643

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0800

Variant links:

Genes affected

UBP1 (HGNC:12507): (upstream binding protein 1) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of viral transcription and positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

UBP1 links:

FBXL2 (HGNC:13598): (F-box and leucine rich repeat protein 2) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains 12 tandem leucine-rich repeats. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

FBXL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBP1	NM_014517.5 linkuse as main transcript	c.1031+7A>C		splice_region_variant, intron_variant		ENST00000283629.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBP1	ENST00000283629.8 linkuse as main transcript	c.1031+7A>C		splice_region_variant, intron_variant		1	NM_014517.5	P3	Q9NZI7-1

Frequencies

GnomAD3 genomes

AF:

0.617

AC:

93611

AN:

151724

Hom.:

29881

Cov.:

show subpopulations

Gnomad AFR

AF:

0.509

Gnomad AMI

AF:

0.845

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.716

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.605

Gnomad NFE

AF:

0.715

Gnomad OTH

AF:

0.626

GnomAD3 exomes

AF:

0.618

AC:

114080

AN:

184548

Hom.:

37015

AF XY:

0.633

AC XY:

62903

AN XY:

99304

show subpopulations

Gnomad AFR exome

AF:

0.497

Gnomad AMR exome

AF:

0.358

Gnomad ASJ exome

AF:

0.719

Gnomad EAS exome

AF:

0.376

Gnomad SAS exome

AF:

0.639

Gnomad FIN exome

AF:

0.651

Gnomad NFE exome

AF:

0.720

Gnomad OTH exome

AF:

0.644

GnomAD4 exome

AF:

0.687

AC:

957650

AN:

1393396

Hom.:

333925

Cov.:

AF XY:

0.687

AC XY:

473271

AN XY:

688702

show subpopulations

Gnomad4 AFR exome

AF:

0.497

Gnomad4 AMR exome

AF:

0.371

Gnomad4 ASJ exome

AF:

0.713

Gnomad4 EAS exome

AF:

0.459

Gnomad4 SAS exome

AF:

0.632

Gnomad4 FIN exome

AF:

0.658

Gnomad4 NFE exome

AF:

0.715

Gnomad4 OTH exome

AF:

0.664

GnomAD4 genome

AF:

0.617

AC:

93650

AN:

151842

Hom.:

29895

Cov.:

AF XY:

0.610

AC XY:

45266

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.509

Gnomad4 AMR

AF:

0.485

Gnomad4 ASJ

AF:

0.716

Gnomad4 EAS

AF:

0.402

Gnomad4 SAS

AF:

0.619

Gnomad4 FIN

AF:

0.646

Gnomad4 NFE

AF:

0.715

Gnomad4 OTH

AF:

0.619

Alfa

AF:

0.688

Hom.:

34991

Bravo

AF:

0.594

Asia WGS

AF:

0.472

AC:

1642

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.6

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.028

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over