16-1324523-A-G

Variant names:

• chr16-1324523-A-G
• rs761059
• NM_003345.5:c.414-207A>G

Variant summary

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

The NM_003345.5(UBE2I):​c.414-207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,132 control chromosomes in the GnomAD database, including 28,367 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 0.61 (28367 hom., cov: 34)
• Consequence: UBE2I NM_003345.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 10 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2I	NM_003345.5	c.414-207A>G		intron_variant	Intron 6 of 6	ENST00000397514.8	NP_003336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2I	ENST00000397514.8	c.414-207A>G		intron_variant	Intron 6 of 6	1	NM_003345.5	ENSP00000380649.3

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92322 AN: 152014 Hom.: 28354 Cov.: 34

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.607 AC: 92371 AN: 152132 Hom.: 28367 Cov.: 34 AF XY: 0.613 AC XY: 45604 AN XY: 74392

African (AFR) AF: 0.605 AC: 25121 AN: 41514

American (AMR) AF: 0.599 AC: 9160 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1612 AN: 3472

East Asian (EAS) AF: 0.833 AC: 4295 AN: 5156

South Asian (SAS) AF: 0.698 AC: 3366 AN: 4822

European-Finnish (FIN) AF: 0.701 AC: 7432 AN: 10602

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39455 AN: 67946

Other (OTH) AF: 0.594 AC: 1256 AN: 2114

Alfa AF: 0.583 Hom.: 12235

Bravo AF: 0.599

Asia WGS AF: 0.743 AC: 2583 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	0.46
DANN	Benign	0.21
PhyloP100		-1.6
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: rs761059; hg19: chr16-1374524;