chr17-76405440-C-T

Position:

• chr17-76405440-C-T

Variant summary

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

The NM_022066.4(UBE2O):​c.477+73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,523,032 control chromosomes in the GnomAD database, including 83,452 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 0.40 (14150 hom., cov: 30)
  • Exomes 𝑓: 0.30 (69302 hom.)
• Consequence: UBE2O NM_022066.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

Genes affected

UBE2O (HGNC:29554): (ubiquitin conjugating enzyme E2 O) Enables ubiquitin conjugating enzyme activity and ubiquitin protein ligase activity. Involved in positive regulation of BMP signaling pathway; protein ubiquitination; and retrograde transport, endosome to Golgi. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

UBE2O (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2O	NM_022066.4	c.477+73G>A		intron_variant		ENST00000319380.12	NP_071349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2O	ENST00000319380.12	c.477+73G>A		intron_variant		1	NM_022066.4	ENSP00000323687.6
UBE2O	ENST00000586409.5	n.477+73G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60885 AN: 151552 Hom.: 14103 Cov.: 30

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.304 AC: 417248 AN: 1371362 Hom.: 69302 Cov.: 22 AF XY: 0.307 AC XY: 208926 AN XY: 681178

Gnomad4 AFR exome AF: 0.638

Gnomad4 AMR exome AF: 0.417

Gnomad4 ASJ exome AF: 0.388

Gnomad4 EAS exome AF: 0.604

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.242

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.341

GnomAD4 genome AF: 0.402 AC: 60995 AN: 151670 Hom.: 14150 Cov.: 30 AF XY: 0.402 AC XY: 29791 AN XY: 74140

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.419

Alfa AF: 0.310 Hom.: 4309

Bravo AF: 0.426

Asia WGS AF: 0.511 AC: 1776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs445683; hg19: chr17-74401522;