rs11248866

Positions:

• chr16-1315340-G-A
• chr16-1315340-G-C

Variant summary

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

The NM_003345.5(UBE2I):​c.151-314G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 400,680 control chromosomes in the GnomAD database, including 74,023 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 0.53 (23681 hom., cov: 34)
  • Exomes 𝑓: 0.63 (50342 hom.)
• Consequence: UBE2I NM_003345.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

UBE2I (HGNC:12485): (ubiquitin conjugating enzyme E2 I) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. Four alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2I	NM_003345.5	c.151-314G>A		intron_variant		ENST00000397514.8	NP_003336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2I	ENST00000397514.8	c.151-314G>A		intron_variant		1	NM_003345.5	ENSP00000380649	P1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80750 AN: 151976 Hom.: 23685 Cov.: 34

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.550

GnomAD4 exome AF: 0.625 AC: 155406 AN: 248586 Hom.: 50342 Cov.: 0 AF XY: 0.627 AC XY: 82332 AN XY: 131228

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.612

Gnomad4 EAS exome AF: 0.897

Gnomad4 SAS exome AF: 0.644

Gnomad4 FIN exome AF: 0.674

Gnomad4 NFE exome AF: 0.616

Gnomad4 OTH exome AF: 0.608

GnomAD4 genome AF: 0.531 AC: 80753 AN: 152094 Hom.: 23681 Cov.: 34 AF XY: 0.539 AC XY: 40070 AN XY: 74344

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.902

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.553

Alfa AF: 0.559 Hom.: 3132

Bravo AF: 0.511

Asia WGS AF: 0.767 AC: 2666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11248866; hg19: chr16-1365341; COSMIC: COSV57648693; COSMIC: COSV57648693;