rs4958217

Positions:

• chr5-134163895-A-C
• chr5-134163895-A-T

Variant summary

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

The NM_170679.3(SKP1):​c.172-2765T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 152,128 control chromosomes in the GnomAD database, including 61,086 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 0.89 (61086 hom., cov: 30)
• Consequence: SKP1 NM_170679.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

SKP1 (HGNC:10899): (S-phase kinase associated protein 1) This gene encodes a component of SCF complexes, which are composed of this protein, cullin 1, a ring-box protein, and one member of the F-box family of proteins. This protein binds directly to the F-box motif found in F-box proteins. SCF complexes are involved in the regulated ubiquitination of specific protein substrates, which targets them for degradation by the proteosome. Specific F-box proteins recognize different target protein(s), and many specific SCF substrates have been identified including regulators of cell cycle progression and development. Studies have also characterized the protein as an RNA polymerase II elongation factor. Alternative splicing of this gene results in two transcript variants. A related pseudogene has been identified on chromosome 7. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKP1	NM_170679.3	c.172-2765T>G		intron_variant		ENST00000353411.11	NP_733779.1
SKP1	NM_006930.4	c.172-2765T>G		intron_variant			NP_008861.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKP1	ENST00000353411.11	c.172-2765T>G		intron_variant		1	NM_170679.3	ENSP00000231487	P1

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135830 AN: 152010 Hom.: 61050 Cov.: 30

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.905

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

GnomAD4 genome AF: 0.893 AC: 135919 AN: 152128 Hom.: 61086 Cov.: 30 AF XY: 0.890 AC XY: 66211 AN XY: 74384

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.817

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.911

Gnomad4 NFE AF: 0.916

Gnomad4 OTH AF: 0.905

Alfa AF: 0.906 Hom.: 30182

Bravo AF: 0.884

Asia WGS AF: 0.797 AC: 2774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.72
DANN	Benign	0.64

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: rs4958217; hg19: chr5-133499586;