rs7026635

Positions:

• chr9-120787749-G-A
• chr9-120787749-G-T

Variant summary

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

The NM_012164.4(FBXW2):​c.490+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,581,226 control chromosomes in the GnomAD database, including 441,342 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 0.77 (44888 hom., cov: 31)
  • Exomes 𝑓: 0.74 (396454 hom.)
• Consequence: FBXW2 NM_012164.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816

Genes affected

FBXW2 (HGNC:13608): (F-box and WD repeat domain containing 2) F-box proteins are an expanding family of eukaryotic proteins characterized by an approximately 40 amino acid motif, the F box. Some F-box proteins have been shown to be critical for the ubiquitin-mediated degradation of cellular regulatory proteins. In fact, F-box proteins are one of the four subunits of ubiquitin protein ligases, called SCFs. SCF ligases bring ubiquitin conjugating enzymes to substrates that are specifically recruited by the different F-box proteins. Mammalian F-box proteins are classified into three groups based on the presence of either WD-40 repeats, leucine-rich repeats, or the presence or absence of other protein-protein interacting domains. This gene encodes the second identified member of the F-box gene family and contains multiple WD-40 repeats. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXW2	NM_012164.4	c.490+20C>T		intron_variant		ENST00000608872.6	NP_036296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXW2	ENST00000608872.6	c.490+20C>T		intron_variant		1	NM_012164.4	ENSP00000476369	P1

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116334 AN: 151982 Hom.: 44838 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.788

GnomAD3 exomes AF: 0.755 AC: 168156 AN: 222800 Hom.: 64197 AF XY: 0.755 AC XY: 91439 AN XY: 121086

Gnomad AFR exome AF: 0.831

Gnomad AMR exome AF: 0.875

Gnomad ASJ exome AF: 0.795

Gnomad EAS exome AF: 0.553

Gnomad SAS exome AF: 0.820

Gnomad FIN exome AF: 0.698

Gnomad NFE exome AF: 0.736

Gnomad OTH exome AF: 0.754

GnomAD4 exome AF: 0.743 AC: 1061699 AN: 1429126 Hom.: 396454 Cov.: 36 AF XY: 0.745 AC XY: 528788 AN XY: 709554

Gnomad4 AFR exome AF: 0.825

Gnomad4 AMR exome AF: 0.867

Gnomad4 ASJ exome AF: 0.787

Gnomad4 EAS exome AF: 0.544

Gnomad4 SAS exome AF: 0.821

Gnomad4 FIN exome AF: 0.704

Gnomad4 NFE exome AF: 0.738

Gnomad4 OTH exome AF: 0.747

GnomAD4 genome AF: 0.766 AC: 116434 AN: 152100 Hom.: 44888 Cov.: 31 AF XY: 0.767 AC XY: 57032 AN XY: 74354

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.787

Alfa AF: 0.749 Hom.: 89593

Bravo AF: 0.777

Asia WGS AF: 0.694 AC: 2415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.48
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: rs7026635; hg19: chr9-123550027;