15-75927944-C-T

Variant names:

• chr15-75927944-C-T
• rs335675
• NM_147188.3:c.629-1940C>T

Variant summary

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

The NM_147188.3(FBXO22):​c.629-1940C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 152,162 control chromosomes in the GnomAD database, including 62,797 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 0.90 (62797 hom., cov: 31)
• Consequence: FBXO22 NM_147188.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• Publications: 3 publications found

Genes affected

FBXO22 (HGNC:13593): (F-box protein 22) 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 the 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 Fbxs class and, as a transcriptional target of the tumor protein p53, is thought to be involved in degradation of specific proteins in response to p53 induction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO22	NM_147188.3	c.629-1940C>T		intron_variant	Intron 5 of 6	ENST00000308275.8	NP_671717.1
FBXO22	NM_012170.4	c.629-1940C>T		intron_variant	Intron 5 of 5		NP_036302.1
FBXO22	NR_037623.2	n.576-1940C>T		intron_variant	Intron 4 of 5
FBXO22	XM_047432382.1	c.317-1940C>T		intron_variant	Intron 4 of 5		XP_047288338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO22	ENST00000308275.8	c.629-1940C>T		intron_variant	Intron 5 of 6	1	NM_147188.3	ENSP00000307833.3

Frequencies

GnomAD3 genomes AF: 0.901 AC: 136959 AN: 152044 Hom.: 62772 Cov.: 31

Gnomad AFR AF: 0.705

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.901 AC: 137029 AN: 152162 Hom.: 62797 Cov.: 31 AF XY: 0.904 AC XY: 67238 AN XY: 74400

African (AFR) AF: 0.704 AC: 29177 AN: 41438

American (AMR) AF: 0.961 AC: 14684 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3434 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5181 AN: 5182

South Asian (SAS) AF: 0.992 AC: 4788 AN: 4828

European-Finnish (FIN) AF: 0.979 AC: 10383 AN: 10606

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.973 AC: 66227 AN: 68036

Other (OTH) AF: 0.925 AC: 1954 AN: 2112

Alfa AF: 0.960 Hom.: 29149

Bravo AF: 0.889

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.32
Mutation Taster		=99/1	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: rs335675; hg19: chr15-76220285;