rs2272152

Positions:

• chr3-33412850-G-A
• chr3-33412850-G-T

Variant summary

Our verdict is Benign. Variant got -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

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: This place is a probable branch point but likely benign (scored 3 / 10). 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBP1	NM_014517.5	c.343-23C>T		intron_variant		ENST00000283629.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBP1	ENST00000283629.8	c.343-23C>T		intron_variant		1	NM_014517.5	P3

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

GnomAD3 exomes AF: 0.255 AC: 63895 AN: 250610 Hom.: 10164 AF XY: 0.241 AC XY: 32672 AN XY: 135384

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 SAS exome AF: 0.221

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

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.253

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.211

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

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.256

Alfa AF: 0.182 Hom.: 1489

Bravo AF: 0.270

Asia WGS AF: 0.385 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.3
DANN	Benign	0.72
BranchPoint Hunter		3.0

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: rs2272152; hg19: chr3-33454342; COSMIC: COSV52144409; COSMIC: COSV52144409;