rs7715070

Variant names:

• chr5-36171831-T-G
• rs7715070
• NM_005983.4:c.901+98T>G

Variant summary

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

The NM_005983.4(SKP2):​c.901+98T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 1,220,382 control chromosomes in the GnomAD database, including 15,401 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 0.21 (7773 hom., cov: 32)
  • Exomes 𝑓: 0.075 (7628 hom.)
• Consequence: SKP2 NM_005983.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKP2	NM_005983.4	c.901+98T>G		intron_variant	Intron 7 of 9	ENST00000274255.11	NP_005974.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKP2	ENST00000274255.11	c.901+98T>G		intron_variant	Intron 7 of 9	1	NM_005983.4	ENSP00000274255.6

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31922 AN: 152028 Hom.: 7732 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0535

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0528

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.0753 AC: 80443 AN: 1068234 Hom.: 7628 AF XY: 0.0757 AC XY: 40824 AN XY: 539330

Gnomad4 AFR exome AF: 0.621

Gnomad4 AMR exome AF: 0.0681

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.0486

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.0385

Gnomad4 NFE exome AF: 0.0525

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.210 AC: 32027 AN: 152148 Hom.: 7773 Cov.: 32 AF XY: 0.205 AC XY: 15239 AN XY: 74400

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0534

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.0325

Gnomad4 NFE AF: 0.0528

Gnomad4 OTH AF: 0.178

Alfa AF: 0.142 Hom.: 799

Bravo AF: 0.233

Asia WGS AF: 0.162 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.4
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7715070; hg19: chr5-36171933;