chr16-1314280-T-C

Position:

• chr16-1314280-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003345.5(UBE2I):​c.67-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 1,613,608 control chromosomes in the GnomAD database, including 642,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64128 hom., cov: 29)
  • Exomes 𝑓: 0.89 (578784 hom.)
• Consequence: UBE2I NM_003345.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.200

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-1314280-T-C is Benign according to our data. Variant chr16-1314280-T-C is described in ClinVar as [Benign]. Clinvar id is 1296955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
UBE2I	NM_003345.5	c.67-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000397514.8	NP_003336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2I	ENST00000397514.8	c.67-13T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003345.5	ENSP00000380649	P1

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139391 AN: 151922 Hom.: 64064 Cov.: 29

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.929

GnomAD3 exomes AF: 0.918 AC: 230511 AN: 251094 Hom.: 106061 AF XY: 0.916 AC XY: 124352 AN XY: 135824

Gnomad AFR exome AF: 0.966

Gnomad AMR exome AF: 0.954

Gnomad ASJ exome AF: 0.879

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.939

Gnomad FIN exome AF: 0.913

Gnomad NFE exome AF: 0.886

Gnomad OTH exome AF: 0.908

GnomAD4 exome AF: 0.889 AC: 1299723 AN: 1461568 Hom.: 578784 Cov.: 50 AF XY: 0.890 AC XY: 647104 AN XY: 727098

Gnomad4 AFR exome AF: 0.968

Gnomad4 AMR exome AF: 0.950

Gnomad4 ASJ exome AF: 0.878

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.937

Gnomad4 FIN exome AF: 0.913

Gnomad4 NFE exome AF: 0.875

Gnomad4 OTH exome AF: 0.896

GnomAD4 genome AF: 0.918 AC: 139514 AN: 152040 Hom.: 64128 Cov.: 29 AF XY: 0.920 AC XY: 68394 AN XY: 74306

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.913

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.930

Alfa AF: 0.888 Hom.: 13657

Bravo AF: 0.922

Asia WGS AF: 0.975 AC: 3391 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.6
DANN	Benign	0.19

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: rs4984806; hg19: chr16-1364281;