rs9048

Variant names:

• chr6-89327862-G-A
• rs9048
• NM_016021.3:c.*1817C>T

Variant summary

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

The NM_016021.3(UBE2J1):​c.*1817C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,176 control chromosomes in the GnomAD database, including 1,815 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 0.14 (1815 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBE2J1 NM_016021.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 8 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2J1	NM_016021.3	c.*1817C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000435041.3	NP_057105.2
UBE2J1	XM_011535887.3	c.*1817C>T		3_prime_UTR_variant	Exon 7 of 7		XP_011534189.1
UBE2J1	XM_011535888.4	c.*2096C>T		3_prime_UTR_variant	Exon 8 of 8		XP_011534190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2J1	ENST00000435041.3	c.*1817C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_016021.3	ENSP00000451261.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21684 AN: 152058 Hom.: 1814 Cov.: 32

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.162

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.142 AC: 21685 AN: 152176 Hom.: 1815 Cov.: 32 AF XY: 0.145 AC XY: 10790 AN XY: 74394

African (AFR) AF: 0.0691 AC: 2872 AN: 41552

American (AMR) AF: 0.121 AC: 1854 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3472

East Asian (EAS) AF: 0.100 AC: 519 AN: 5178

South Asian (SAS) AF: 0.267 AC: 1287 AN: 4816

European-Finnish (FIN) AF: 0.164 AC: 1740 AN: 10592

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.176 AC: 11935 AN: 67984

Other (OTH) AF: 0.168 AC: 355 AN: 2114

Alfa AF: 0.167 Hom.: 3915

Bravo AF: 0.133

Asia WGS AF: 0.201 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.51
PhyloP100		1.9
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: rs9048; hg19: chr6-90037581;