3-33412850-G-A

Variant names:

• chr3-33412850-G-A
• rs2272152
• NM_014517.5:c.343-23C>T

Variant summary

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

The NM_014517.5(UBP1):​c.343-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,536,218 control chromosomes in the GnomAD database, including 36,235 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.26 (5859 hom., cov: 31)
  • Exomes 𝑓: 0.19 (30376 hom.)
• Consequence: UBP1 NM_014517.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• Publications: 11 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBP1	NM_014517.5	MANE Select	c.343-23C>T		intron	N/A	NP_055332.3
	UBP1	NM_001128161.2		c.343-23C>T		intron	N/A	NP_001121633.1
	UBP1	NM_001128160.2		c.343-23C>T		intron	N/A	NP_001121632.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBP1	ENST00000283629.8	TSL:1 MANE Select	c.343-23C>T		intron	N/A	ENSP00000283629.3
	UBP1	ENST00000283628.9	TSL:2	c.343-23C>T		intron	N/A	ENSP00000283628.5
	UBP1	ENST00000447368.6	TSL:2	c.343-23C>T		intron	N/A	ENSP00000395558.2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38855 AN: 151894 Hom.: 5832 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.248

GnomAD2 exomes AF: 0.255 AC: 63895 AN: 250610 AF XY: 0.241

Gnomad AFR exome AF: 0.377

Gnomad AMR exome AF: 0.434

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.505

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.194 AC: 268488 AN: 1384206 Hom.: 30376 Cov.: 22 AF XY: 0.193 AC XY: 133663 AN XY: 692896

African (AFR) AF: 0.373 AC: 11938 AN: 32032

American (AMR) AF: 0.425 AC: 18949 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4390 AN: 25610

East Asian (EAS) AF: 0.442 AC: 17337 AN: 39262

South Asian (SAS) AF: 0.219 AC: 18547 AN: 84662

European-Finnish (FIN) AF: 0.253 AC: 13500 AN: 53322

Middle Eastern (MID) AF: 0.169 AC: 949 AN: 5630

European-Non Finnish (NFE) AF: 0.164 AC: 170664 AN: 1041314

Other (OTH) AF: 0.211 AC: 12214 AN: 57786

GnomAD4 genome AF: 0.256 AC: 38918 AN: 152012 Hom.: 5859 Cov.: 31 AF XY: 0.262 AC XY: 19460 AN XY: 74298

African (AFR) AF: 0.361 AC: 14959 AN: 41466

American (AMR) AF: 0.345 AC: 5262 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3466

East Asian (EAS) AF: 0.472 AC: 2435 AN: 5156

South Asian (SAS) AF: 0.228 AC: 1101 AN: 4822

European-Finnish (FIN) AF: 0.267 AC: 2817 AN: 10544

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.162 AC: 11039 AN: 67974

Other (OTH) AF: 0.256 AC: 539 AN: 2108

Alfa AF: 0.185 Hom.: 2115

Bravo AF: 0.270

Asia WGS AF: 0.385 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.3
DANN	Benign	0.72
PhyloP100		-0.16
BranchPoint Hunter		3.0
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: rs2272152; hg19: chr3-33454342; COSMIC: COSV52144409; COSMIC: COSV52144409;