8-28434935-G-T

Position:

• chr8-28434935-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO16	NM_172366.4	c.844-5532C>A		intron_variant		ENST00000380254.7	NP_758954.1
FBXO16	NM_001258211.2	c.808-5532C>A		intron_variant			NP_001245140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO16	ENST00000380254.7	c.844-5532C>A		intron_variant		1	NM_172366.4	ENSP00000369604.2

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

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.0653

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.0904

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00260

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.00459 Hom.: 7

Bravo AF: 0.113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.83
DANN	Benign	0.45

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: rs6558058; hg19: chr8-28292452;