rs7731023

Variant names:

• chr5-36181525-A-G
• rs7731023
• NM_005983.4:c.1062-293A>G

Variant summary

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

The NM_005983.4(SKP2):​c.1062-293A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,136 control chromosomes in the GnomAD database, including 17,026 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 0.43 (17026 hom., cov: 32)
• Consequence: SKP2 NM_005983.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645
• Publications: 25 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKP2	NM_005983.4	MANE Select	c.1062-293A>G		intron	N/A	NP_005974.2
	SKP2	NM_032637.4		c.1062-2315A>G		intron	N/A	NP_116026.1	Q13309-2
	SKP2	NM_001243120.2		c.420-293A>G		intron	N/A	NP_001230049.1	Q13309-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKP2	ENST00000274255.11	TSL:1 MANE Select	c.1062-293A>G		intron	N/A	ENSP00000274255.6	Q13309-1
	SKP2	ENST00000274254.9	TSL:1	c.1062-2315A>G		intron	N/A	ENSP00000274254.5	Q13309-2
	SKP2	ENST00000678580.1		c.*2912A>G		3_prime_UTR	Exon 10 of 10	ENSP00000504064.1	D6R9R7

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65061 AN: 152018 Hom.: 17029 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.0853

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.428 AC: 65057 AN: 152136 Hom.: 17026 Cov.: 32 AF XY: 0.427 AC XY: 31765 AN XY: 74372

African (AFR) AF: 0.164 AC: 6806 AN: 41510

American (AMR) AF: 0.437 AC: 6674 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1828 AN: 3468

East Asian (EAS) AF: 0.0857 AC: 444 AN: 5180

South Asian (SAS) AF: 0.255 AC: 1229 AN: 4828

European-Finnish (FIN) AF: 0.669 AC: 7079 AN: 10574

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39320 AN: 67976

Other (OTH) AF: 0.424 AC: 898 AN: 2116

Alfa AF: 0.520 Hom.: 40467

Bravo AF: 0.401

Asia WGS AF: 0.170 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.73
PhyloP100		0.65
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: rs7731023; hg19: chr5-36181627;