rs10507276

Variant names:

• chr12-116948025-G-A
• rs10507276
• NM_153348.3:c.589-1593G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-116948025-G-A
• chr12-116948025-G-C

Variant summary

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

The NM_153348.3(FBXW8):​c.589-1593G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,120 control chromosomes in the GnomAD database, including 1,391 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 0.13 (1391 hom., cov: 32)
• Consequence: FBXW8 NM_153348.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXW8	NM_153348.3	c.589-1593G>A		intron_variant	Intron 3 of 10	ENST00000652555.1	NP_699179.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXW8	ENST00000652555.1	c.589-1593G>A		intron_variant	Intron 3 of 10		NM_153348.3	ENSP00000498999.1
FBXW8	ENST00000455858.2	c.391-1593G>A		intron_variant	Intron 3 of 10	1		ENSP00000389144.2
FBXW8	ENST00000309909.11	c.277-1593G>A		intron_variant	Intron 3 of 10	1		ENSP00000310686.6

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20116 AN: 152002 Hom.: 1391 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0848

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.132 AC: 20132 AN: 152120 Hom.: 1391 Cov.: 32 AF XY: 0.130 AC XY: 9656 AN XY: 74368

African (AFR) AF: 0.117 AC: 4851 AN: 41512

American (AMR) AF: 0.114 AC: 1744 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3470

East Asian (EAS) AF: 0.120 AC: 620 AN: 5176

South Asian (SAS) AF: 0.151 AC: 728 AN: 4810

European-Finnish (FIN) AF: 0.0848 AC: 897 AN: 10576

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.150 AC: 10164 AN: 67978

Other (OTH) AF: 0.141 AC: 298 AN: 2106

Alfa AF: 0.133 Hom.: 788

Bravo AF: 0.134

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.76
PhyloP100		-0.27
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: rs10507276; hg19: chr12-117385830;