chr10-58366117-C-T

Position:

• chr10-58366117-C-T

Variant summary

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

The ENST00000373910.9(UBE2D1):​c.304+1241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,028 control chromosomes in the GnomAD database, including 15,578 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 0.45 (15578 hom., cov: 33)
• Consequence: UBE2D1 ENST00000373910.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

Genes affected

UBE2D1 (HGNC:12474): (ubiquitin conjugating enzyme E2 D1) 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 closely related to a stimulator of iron transport (SFT), and is up-regulated in hereditary hemochromatosis. It also functions in the ubiquitination of the tumor-suppressor protein p53 and the hypoxia-inducible transcription factor HIF1alpha by interacting with the E1 ubiquitin-activating enzyme and the E3 ubiquitin-protein ligases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2D1	NM_003338.5	c.304+1241C>T		intron_variant		ENST00000373910.9	NP_003329.1
UBE2D1	NM_001204880.2	c.190+1241C>T		intron_variant			NP_001191809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2D1	ENST00000373910.9	c.304+1241C>T		intron_variant		1	NM_003338.5	ENSP00000363019	P1
UBE2D1	ENST00000615793.1	c.190+1241C>T		intron_variant		2		ENSP00000479814
UBE2D1	ENST00000473824.1	n.421+1241C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68029 AN: 151910 Hom.: 15551 Cov.: 33

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.448 AC: 68106 AN: 152028 Hom.: 15578 Cov.: 33 AF XY: 0.444 AC XY: 32997 AN XY: 74298

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.459

Alfa AF: 0.417 Hom.: 2140

Bravo AF: 0.458

Asia WGS AF: 0.394 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.50

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: rs11006122; hg19: chr10-60125877;