4-39767966-A-G

Variant names:

• chr4-39767966-A-G
• rs305124
• NM_005339.5:c.300-6868A>G

Variant summary

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

The NM_005339.5(UBE2K):​c.300-6868A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,004 control chromosomes in the GnomAD database, including 4,098 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 0.18 (4098 hom., cov: 31)
• Consequence: UBE2K NM_005339.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

Genes affected

UBE2K (HGNC:4914): (ubiquitin conjugating enzyme E2 K) The protein encoded by this gene belongs to the ubiquitin-conjugating enzyme family. This protein interacts with RING finger proteins, and it can ubiquitinate huntingtin, the gene product for Huntington's disease. Known functions for this protein include a role in aggregate formation of expanded polyglutamine proteins and the suppression of apoptosis in polyglutamine diseases, a role in the dislocation of newly synthesized MHC class I heavy chains from the endoplasmic reticulum, and involvement in foam cell formation. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2K	NM_005339.5	c.300-6868A>G		intron_variant	Intron 4 of 6	ENST00000261427.10	NP_005330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2K	ENST00000261427.10	c.300-6868A>G		intron_variant	Intron 4 of 6	1	NM_005339.5	ENSP00000261427.5

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26830 AN: 151886 Hom.: 4082 Cov.: 31

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.0686

Gnomad SAS AF: 0.0302

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.177 AC: 26886 AN: 152004 Hom.: 4098 Cov.: 31 AF XY: 0.174 AC XY: 12913 AN XY: 74282

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0502

Gnomad4 EAS AF: 0.0686

Gnomad4 SAS AF: 0.0303

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0827

Gnomad4 OTH AF: 0.147

Alfa AF: 0.0986 Hom.: 577

Bravo AF: 0.187

Asia WGS AF: 0.0640 AC: 224 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	5.1
DANN	Benign	0.78

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: rs305124; hg19: chr4-39769586;