8-28434935-G-T

Variant names:

• chr8-28434935-G-T
• rs6558058
• NM_172366.4:c.844-5532C>A

Variant summary

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

The NM_172366.4(FBXO16):​c.844-5532C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 152,214 control chromosomes in the GnomAD database, including 1,986 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 0.098 (1986 hom., cov: 32)
• Consequence: FBXO16 NM_172366.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 1 publications found

Genes affected

FBXO16 (HGNC:13618): (F-box protein 16) This gene encodes a member of the F-box protein family, members of which are 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 three 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 Fbx class. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ENSG00000253567 (HGNC:58255):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172366.4. 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
	FBXO16	NM_172366.4	MANE Select	c.844-5532C>A		intron	N/A	NP_758954.1
	FBXO16	NM_001258211.2		c.808-5532C>A		intron	N/A	NP_001245140.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO16	ENST00000380254.7	TSL:1 MANE Select	c.844-5532C>A		intron	N/A	ENSP00000369604.2
	FBXO16	ENST00000518734.5	TSL:1	c.808-5532C>A		intron	N/A	ENSP00000429687.1
	FBXO16	ENST00000346498.6	TSL:5	c.808-6199C>A		intron	N/A	ENSP00000341416.2

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14924 AN: 152094 Hom.: 1978 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00260

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.0982 AC: 14948 AN: 152214 Hom.: 1986 Cov.: 32 AF XY: 0.0990 AC XY: 7366 AN XY: 74426

African (AFR) AF: 0.290 AC: 12012 AN: 41474

American (AMR) AF: 0.0653 AC: 998 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.215 AC: 1112 AN: 5172

South Asian (SAS) AF: 0.0904 AC: 437 AN: 4832

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10626

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00260 AC: 177 AN: 68026

Other (OTH) AF: 0.0781 AC: 165 AN: 2114

Alfa AF: 0.00459 Hom.: 7

Bravo AF: 0.113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.83
DANN	Benign	0.45
PhyloP100		-0.50
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: rs6558058; hg19: chr8-28292452;