rs1357540

Variant names:

• chr3-33438490-T-C
• rs1357540
• NM_014517.5:c.113+1246A>G

Variant summary

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

The NM_014517.5(UBP1):​c.113+1246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,088 control chromosomes in the GnomAD database, including 5,990 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 0.26 (5990 hom., cov: 32)
• Consequence: UBP1 NM_014517.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 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.113+1246A>G		intron	N/A	NP_055332.3
	UBP1	NM_001128161.2		c.113+1246A>G		intron	N/A	NP_001121633.1	Q9NZI7-1
	UBP1	NM_001128160.2		c.113+1246A>G		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.113+1246A>G		intron	N/A	ENSP00000283629.3	Q9NZI7-1
	UBP1	ENST00000283628.9	TSL:2	c.113+1246A>G		intron	N/A	ENSP00000283628.5	Q9NZI7-1
	UBP1	ENST00000908179.1		c.113+1246A>G		intron	N/A	ENSP00000578238.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39233 AN: 151970 Hom.: 5962 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.258 AC: 39297 AN: 152088 Hom.: 5990 Cov.: 32 AF XY: 0.264 AC XY: 19666 AN XY: 74354

African (AFR) AF: 0.368 AC: 15259 AN: 41470

American (AMR) AF: 0.346 AC: 5284 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 602 AN: 3462

East Asian (EAS) AF: 0.471 AC: 2436 AN: 5174

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4820

European-Finnish (FIN) AF: 0.267 AC: 2820 AN: 10564

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11048 AN: 67992

Other (OTH) AF: 0.258 AC: 545 AN: 2110

Alfa AF: 0.187 Hom.: 1600

Bravo AF: 0.273

Asia WGS AF: 0.388 AC: 1347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		0.15
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: rs1357540; hg19: chr3-33479982;