rs40030

Positions:

• chr5-36176772-G-A
• chr5-36176772-G-C
• chr5-36176772-G-T

Variant summary

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

The ENST00000274255.11(SKP2):​c.902-193G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,672 control chromosomes in the GnomAD database, including 34,349 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 0.61 (34349 hom., cov: 31)
• Consequence: SKP2 ENST00000274255.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKP2	NM_005983.4	c.902-193G>A		intron_variant		ENST00000274255.11	NP_005974.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKP2	ENST00000274255.11	c.902-193G>A		intron_variant		1	NM_005983.4	ENSP00000274255	P1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93274 AN: 151554 Hom.: 34353 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.905

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.615 AC: 93276 AN: 151672 Hom.: 34349 Cov.: 31 AF XY: 0.616 AC XY: 45640 AN XY: 74144

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.905

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.649

Alfa AF: 0.555 Hom.: 3296

Bravo AF: 0.577

Asia WGS AF: 0.445 AC: 1550 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.61
DANN	Benign	0.67

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: rs40030; hg19: chr5-36176874;