16-1320302-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003345.5(UBE2I):c.333+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 1,612,110 control chromosomes in the GnomAD database, including 643,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.92 (64097 hom., cov: 31)
  • Exomes 𝑓: 0.89 (579067 hom.)
• Consequence: UBE2I NM_003345.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.556

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-1320302-T-C is Benign according to our data. Variant chr16-1320302-T-C is described in ClinVar as [Benign]. Clinvar id is 1260109.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2I	NM_003345.5	c.333+19T>C		intron_variant		ENST00000397514.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2I	ENST00000397514.8	c.333+19T>C		intron_variant		1	NM_003345.5	P1
	ENST00000567829.1	n.515A>G		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139308 AN: 151806 Hom.: 64033 Cov.: 31

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.931

GnomAD3 exomes AF: 0.918 AC: 229492 AN: 249876 Hom.: 105615 AF XY: 0.916 AC XY: 123823 AN XY: 135206

Gnomad AFR exome AF: 0.966

Gnomad AMR exome AF: 0.954

Gnomad ASJ exome AF: 0.886

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.939

Gnomad FIN exome AF: 0.914

Gnomad NFE exome AF: 0.886

Gnomad OTH exome AF: 0.909

GnomAD4 exome AF: 0.890 AC: 1299452 AN: 1460186 Hom.: 579067 Cov.: 38 AF XY: 0.891 AC XY: 646937 AN XY: 726360

Gnomad4 AFR exome AF: 0.968

Gnomad4 AMR exome AF: 0.951

Gnomad4 ASJ exome AF: 0.885

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.937

Gnomad4 FIN exome AF: 0.913

Gnomad4 NFE exome AF: 0.876

Gnomad4 OTH exome AF: 0.897

GnomAD4 genome AF: 0.918 AC: 139431 AN: 151924 Hom.: 64097 Cov.: 31 AF XY: 0.921 AC XY: 68322 AN XY: 74220

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.885

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.931

Alfa AF: 0.890 Hom.: 11111

Bravo AF: 0.922

Asia WGS AF: 0.975 AC: 3389 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.2
Dann	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs909916; hg19: chr16-1370303;