6-89348950-C-T

Position:

• chr6-89348950-C-T

Variant summary

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

The NM_016021.3(UBE2J1):​c.31+3589G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,008 control chromosomes in the GnomAD database, including 9,198 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 0.33 (9198 hom., cov: 32)
• Consequence: UBE2J1 NM_016021.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314

Genes affected

UBE2J1 (HGNC:17598): (ubiquitin conjugating enzyme E2 J1) 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. This enzyme is located in the membrane of the endoplasmic reticulum (ER) and may contribute to quality control ER-associated degradation by the ubiquitin-proteasome system. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2J1	NM_016021.3	c.31+3589G>A		intron_variant		ENST00000435041.3	NP_057105.2
UBE2J1	XM_011535887.3	c.31+3589G>A		intron_variant			XP_011534189.1
UBE2J1	XM_011535888.4	c.31+3589G>A		intron_variant			XP_011534190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2J1	ENST00000435041.3	c.31+3589G>A		intron_variant		1	NM_016021.3	ENSP00000451261	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49400 AN: 151890 Hom.: 9174 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.326 AC: 49482 AN: 152008 Hom.: 9198 Cov.: 32 AF XY: 0.331 AC XY: 24571 AN XY: 74298

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.290

Alfa AF: 0.266 Hom.: 2753

Bravo AF: 0.331

Asia WGS AF: 0.477 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.37

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: rs9351207; hg19: chr6-90058669; COSMIC: COSV70562494;