12-116999056-C-T

Variant names:

• chr12-116999056-C-T
• rs4767492
• NM_153348.3:c.1239+10187C>T

Variant summary

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

The NM_153348.3(FBXW8):​c.1239+10187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 152,116 control chromosomes in the GnomAD database, including 63,432 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 0.91 (63432 hom., cov: 33)
• Consequence: FBXW8 NM_153348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 6 publications found

Genes affected

FBXW8 (HGNC:13597): (F-box and WD repeat domain containing 8) 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 contains a WD-40 domain, in addition to an F-box motif, so it belongs to the Fbw class. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153348.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXW8	NM_153348.3	MANE Select	c.1239+10187C>T		intron	N/A	NP_699179.2
	FBXW8	NM_012174.2		c.1041+10187C>T		intron	N/A	NP_036306.1	Q8N3Y1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXW8	ENST00000652555.1	MANE Select	c.1239+10187C>T		intron	N/A	ENSP00000498999.1	Q8N3Y1-1
	FBXW8	ENST00000455858.2	TSL:1	c.1041+10187C>T		intron	N/A	ENSP00000389144.2	Q8N3Y1-2
	FBXW8	ENST00000309909.11	TSL:1	c.927+10187C>T		intron	N/A	ENSP00000310686.6	A0A499FIY5

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138789 AN: 151998 Hom.: 63384 Cov.: 33

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.913 AC: 138893 AN: 152116 Hom.: 63432 Cov.: 33 AF XY: 0.915 AC XY: 68079 AN XY: 74366

African (AFR) AF: 0.892 AC: 37020 AN: 41502

American (AMR) AF: 0.936 AC: 14302 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2980 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5182 AN: 5186

South Asian (SAS) AF: 0.962 AC: 4642 AN: 4826

European-Finnish (FIN) AF: 0.932 AC: 9862 AN: 10584

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61925 AN: 67954

Other (OTH) AF: 0.900 AC: 1904 AN: 2116

Alfa AF: 0.910 Hom.: 98453

Bravo AF: 0.912

Asia WGS AF: 0.964 AC: 3354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.85
PhyloP100		-1.3
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: rs4767492; hg19: chr12-117436861;