NM_005983.4:c.280+4671T>C

Variant names:

• chr5-36157713-T-C
• rs33678
• NM_005983.4:c.280+4671T>C

Variant summary

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

The NM_005983.4(SKP2):​c.280+4671T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,120 control chromosomes in the GnomAD database, including 45,138 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 0.75 (45138 hom., cov: 32)
• Consequence: SKP2 NM_005983.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 13 publications found

Genes affected

SKP2 (HGNC:10901): (S-phase kinase associated protein 2) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class; in addition to an F-box, this protein contains 10 tandem leucine-rich repeats. This protein is an essential element of the cyclin A-CDK2 S-phase kinase. It specifically recognizes phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S phase and interacts with S-phase kinase-associated protein 1 (SKP1 or p19). In addition, this gene is established as a protooncogene causally involved in the pathogenesis of lymphomas. Alternative splicing of this gene generates three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKP2	NM_005983.4	c.280+4671T>C		intron_variant	Intron 2 of 9	ENST00000274255.11	NP_005974.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKP2	ENST00000274255.11	c.280+4671T>C		intron_variant	Intron 2 of 9	1	NM_005983.4	ENSP00000274255.6

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113687 AN: 152002 Hom.: 45120 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.748 AC: 113750 AN: 152120 Hom.: 45138 Cov.: 32 AF XY: 0.747 AC XY: 55546 AN XY: 74392

African (AFR) AF: 0.510 AC: 21135 AN: 41446

American (AMR) AF: 0.699 AC: 10684 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3011 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2131 AN: 5176

South Asian (SAS) AF: 0.731 AC: 3528 AN: 4826

European-Finnish (FIN) AF: 0.945 AC: 10017 AN: 10596

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.890 AC: 60538 AN: 68004

Other (OTH) AF: 0.778 AC: 1644 AN: 2112

Alfa AF: 0.828 Hom.: 98529

Bravo AF: 0.719

Asia WGS AF: 0.608 AC: 2115 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	0.54
DANN	Benign	0.47
PhyloP100		-1.1
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: rs33678; hg19: chr5-36157815;