17-76437921-C-T

Variant names:

• chr17-76437921-C-T
• rs1000821
• NM_022066.4:c.417+14804G>A

Variant summary

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

The NM_022066.4(UBE2O):​c.417+14804G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,048 control chromosomes in the GnomAD database, including 10,477 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 0.34 (10477 hom., cov: 31)
• Consequence: UBE2O NM_022066.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 12 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2O	NM_022066.4	c.417+14804G>A		intron_variant	Intron 1 of 17	ENST00000319380.12	NP_071349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2O	ENST00000319380.12	c.417+14804G>A		intron_variant	Intron 1 of 17	1	NM_022066.4	ENSP00000323687.6
UBE2O	ENST00000586409.5	n.417+14804G>A		intron_variant	Intron 1 of 13	2

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51097 AN: 151930 Hom.: 10486 Cov.: 31

Gnomad AFR AF: 0.0875

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.336 AC: 51086 AN: 152048 Hom.: 10477 Cov.: 31 AF XY: 0.336 AC XY: 24946 AN XY: 74318

African (AFR) AF: 0.0872 AC: 3619 AN: 41502

American (AMR) AF: 0.400 AC: 6115 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1323 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1235 AN: 5180

South Asian (SAS) AF: 0.315 AC: 1521 AN: 4826

European-Finnish (FIN) AF: 0.464 AC: 4885 AN: 10538

Middle Eastern (MID) AF: 0.310 AC: 90 AN: 290

European-Non Finnish (NFE) AF: 0.459 AC: 31183 AN: 67934

Other (OTH) AF: 0.334 AC: 706 AN: 2112

Alfa AF: 0.417 Hom.: 37764

Bravo AF: 0.320

Asia WGS AF: 0.293 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.61
PhyloP100		-0.32
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: rs1000821; hg19: chr17-74434003;