3-33398826-C-T

Variant names:

• chr3-33398826-C-T
• rs17030583
• NM_014517.5:c.1180+1363G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014517.5(UBP1):​c.1180+1363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,096 control chromosomes in the GnomAD database, including 7,026 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 0.29 (7026 hom., cov: 33)
• Consequence: UBP1 NM_014517.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 3 publications found

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: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]

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 (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014517.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBP1	NM_014517.5	MANE Select	c.1180+1363G>A		intron	N/A	NP_055332.3
	UBP1	NM_001128161.2		c.1180+1363G>A		intron	N/A	NP_001121633.1	Q9NZI7-1
	UBP1	NM_001128160.2		c.1072+1363G>A		intron	N/A	NP_001121632.1	Q9NZI7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBP1	ENST00000283629.8	TSL:1 MANE Select	c.1180+1363G>A		intron	N/A	ENSP00000283629.3	Q9NZI7-1
	UBP1	ENST00000283628.9	TSL:2	c.1180+1363G>A		intron	N/A	ENSP00000283628.5	Q9NZI7-1
	UBP1	ENST00000908179.1		c.1180+1363G>A		intron	N/A	ENSP00000578238.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44068 AN: 151978 Hom.: 7000 Cov.: 33

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.290 AC: 44125 AN: 152096 Hom.: 7026 Cov.: 33 AF XY: 0.295 AC XY: 21912 AN XY: 74358

African (AFR) AF: 0.374 AC: 15485 AN: 41454

American (AMR) AF: 0.370 AC: 5664 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 720 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2437 AN: 5166

South Asian (SAS) AF: 0.274 AC: 1323 AN: 4824

European-Finnish (FIN) AF: 0.290 AC: 3074 AN: 10584

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14584 AN: 67992

Other (OTH) AF: 0.293 AC: 618 AN: 2112

Alfa AF: 0.241 Hom.: 7402

Bravo AF: 0.302

Asia WGS AF: 0.402 AC: 1396 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.0
DANN	Benign	0.80
PhyloP100		-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: rs17030583; hg19: chr3-33440318;