9-37576451-T-G

Variant names:

• chr9-37576451-T-G
• rs6476643
• ENST00000537239.2:n.*87+12360A>C

Variant summary

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

The ENST00000537239.2(ENSG00000256966):​n.*87+12360A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,214 control chromosomes in the GnomAD database, including 45,385 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 0.77 (45369 hom., cov: 33)
  • Exomes 𝑓: 0.72 (16 hom.)
• Consequence: ENSG00000256966 ENST00000537239.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 6 publications found

Genes affected

ENSG00000256966 (HGNC:):

FBXO10 (HGNC:13589): (F-box protein 10) Members of the F-box protein family, such as FBXO10, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000537239.2. 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
	FBXO10	NM_012166.3	MANE Select	c.-247A>C		upstream_gene	N/A	NP_036298.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000256966	ENST00000537239.2	TSL:5	n.*87+12360A>C		intron	N/A	ENSP00000457849.1
	ENSG00000256966	ENST00000541804.1	TSL:1	n.62+12362A>C		intron	N/A
	ENSG00000256966	ENST00000544475.5	TSL:1	n.122+12302A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117107 AN: 152036 Hom.: 45304 Cov.: 33

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.947

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.762

GnomAD4 exome AF: 0.717 AC: 43 AN: 60 Hom.: 16 AF XY: 0.675 AC XY: 27 AN XY: 40

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.800 AC: 8 AN: 10

Middle Eastern (MID) AF: 0.500 AC: 3 AN: 6

European-Non Finnish (NFE) AF: 0.750 AC: 30 AN: 40

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.770 AC: 117232 AN: 152154 Hom.: 45369 Cov.: 33 AF XY: 0.774 AC XY: 57586 AN XY: 74390

African (AFR) AF: 0.799 AC: 33164 AN: 41520

American (AMR) AF: 0.815 AC: 12467 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2389 AN: 3468

East Asian (EAS) AF: 0.947 AC: 4885 AN: 5160

South Asian (SAS) AF: 0.838 AC: 4046 AN: 4826

European-Finnish (FIN) AF: 0.742 AC: 7859 AN: 10594

Middle Eastern (MID) AF: 0.750 AC: 219 AN: 292

European-Non Finnish (NFE) AF: 0.734 AC: 49876 AN: 67978

Other (OTH) AF: 0.765 AC: 1616 AN: 2112

Alfa AF: 0.760 Hom.: 7859

Bravo AF: 0.780

Asia WGS AF: 0.903 AC: 3141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.7
DANN	Benign	0.72
PhyloP100		-0.11
PromoterAI		0.057	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6476643; hg19: chr9-37576448;