chr5-36157228-G-A

Variant names:

• chr5-36157228-G-A
• rs4440390
• NM_005983.4:c.280+4186G>A

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+4186G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,016 control chromosomes in the GnomAD database, including 40,970 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 0.70 (40970 hom., cov: 31)
• Consequence: SKP2 NM_005983.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005983.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKP2	NM_005983.4	MANE Select	c.280+4186G>A		intron	N/A	NP_005974.2
	SKP2	NM_032637.4		c.280+4186G>A		intron	N/A	NP_116026.1
	SKP2	NM_001243120.2		c.-116+4186G>A		intron	N/A	NP_001230049.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKP2	ENST00000274255.11	TSL:1 MANE Select	c.280+4186G>A		intron	N/A	ENSP00000274255.6
	SKP2	ENST00000274254.9	TSL:1	c.280+4186G>A		intron	N/A	ENSP00000274254.5
	SKP2	ENST00000546211.6	TSL:5	c.281-2545G>A		intron	N/A	ENSP00000443492.3

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105741 AN: 151896 Hom.: 40961 Cov.: 31

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.696 AC: 105777 AN: 152016 Hom.: 40970 Cov.: 31 AF XY: 0.696 AC XY: 51693 AN XY: 74322

African (AFR) AF: 0.366 AC: 15153 AN: 41376

American (AMR) AF: 0.679 AC: 10371 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2943 AN: 3472

East Asian (EAS) AF: 0.412 AC: 2128 AN: 5170

South Asian (SAS) AF: 0.668 AC: 3215 AN: 4812

European-Finnish (FIN) AF: 0.938 AC: 9945 AN: 10606

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.874 AC: 59426 AN: 67990

Other (OTH) AF: 0.734 AC: 1549 AN: 2110

Alfa AF: 0.812 Hom.: 10559

Bravo AF: 0.663

Asia WGS AF: 0.583 AC: 2030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.39
PhyloP100		-0.51
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: rs4440390; hg19: chr5-36157330;