NM_001142958.2:c.333-1683C>G

Variant names:

• chr18-74132341-G-C
• rs8086078
• NM_001142958.2:c.333-1683C>G

Variant summary

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

The NM_001142958.2(FBXO15):​c.333-1683C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 152,106 control chromosomes in the GnomAD database, including 1,501 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 (1501 hom., cov: 33)
• Consequence: FBXO15 NM_001142958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 5 publications found

Genes affected

FBXO15 (HGNC:13617): (F-box protein 15) Members of the F-box protein family, such as FBXO15, 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]

FBXO15 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000301994 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142958.2. 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
	FBXO15	NM_001142958.2	MANE Select	c.333-1683C>G		intron	N/A	NP_001136430.1
	FBXO15	NM_152676.3		c.105-1683C>G		intron	N/A	NP_689889.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO15	ENST00000419743.7	TSL:2 MANE Select	c.333-1683C>G		intron	N/A	ENSP00000393154.2
	FBXO15	ENST00000583443.5	TSL:1	n.*342-1683C>G		intron	N/A	ENSP00000464177.1
	FBXO15	ENST00000582526.1	TSL:3	c.222-1683C>G		intron	N/A	ENSP00000463529.1

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 14841 AN: 151988 Hom.: 1501 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0605

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0590

Gnomad FIN AF: 0.00509

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.0977 AC: 14868 AN: 152106 Hom.: 1501 Cov.: 33 AF XY: 0.0964 AC XY: 7171 AN XY: 74360

African (AFR) AF: 0.249 AC: 10312 AN: 41450

American (AMR) AF: 0.0604 AC: 924 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.116 AC: 600 AN: 5166

South Asian (SAS) AF: 0.0590 AC: 284 AN: 4812

European-Finnish (FIN) AF: 0.00509 AC: 54 AN: 10604

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0319 AC: 2169 AN: 67998

Other (OTH) AF: 0.0903 AC: 191 AN: 2114

Alfa AF: 0.00587 Hom.: 2

Bravo AF: 0.109

Asia WGS AF: 0.109 AC: 377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		-0.029
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: rs8086078; hg19: chr18-71799576;