rs1998576

Positions:

• chr6-89333418-G-A

Variant summary

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

The NM_016021.3(UBE2J1):​c.559-213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,114 control chromosomes in the GnomAD database, including 2,958 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 0.19 (2958 hom., cov: 32)
• Consequence: UBE2J1 NM_016021.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2J1	NM_016021.3	c.559-213C>T		intron_variant		ENST00000435041.3	NP_057105.2
UBE2J1	XM_011535887.3	c.558+1884C>T		intron_variant			XP_011534189.1
UBE2J1	XM_011535888.4	c.559-213C>T		intron_variant			XP_011534190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2J1	ENST00000435041.3	c.559-213C>T		intron_variant		1	NM_016021.3	ENSP00000451261	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29372 AN: 151994 Hom.: 2952 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0916

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.193 AC: 29401 AN: 152114 Hom.: 2958 Cov.: 32 AF XY: 0.193 AC XY: 14362 AN XY: 74342

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.0919

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.204

Alfa AF: 0.192 Hom.: 5979

Bravo AF: 0.189

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.37
DANN	Benign	0.43

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: rs1998576; hg19: chr6-90043137;