3-33402794-T-G

Position:

• chr3-33402794-T-G

Variant summary

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

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

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]

FBXL2 (HGNC:):

ACMG classification

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	Protein	UniProt
UBP1	NM_014517.5	c.1031+7A>C		splice_region_variant, intron_variant		ENST00000283629.8	NP_055332.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBP1	ENST00000283629.8	c.1031+7A>C		splice_region_variant, intron_variant		1	NM_014517.5	ENSP00000283629.3

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93611 AN: 151724 Hom.: 29881 Cov.: 31

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

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.: 28 AF XY: 0.687 AC XY: 473271 AN XY: 688702

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.: 31 AF XY: 0.610 AC XY: 45266 AN XY: 74216

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

Other links and lift over

dbSNP: rs623244; hg19: chr3-33444286; COSMIC: COSV52145541; COSMIC: COSV52145541;