rs9945428

Variant names:

• chr18-74121441-C-A
• rs9945428
• NM_001142958.2:c.1138+1927G>T

Variant summary

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

The NM_001142958.2(FBXO15):​c.1138+1927G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,066 control chromosomes in the GnomAD database, including 11,964 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 0.37 (11964 hom., cov: 33)
• Consequence: FBXO15 NM_001142958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450
• Publications: 8 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 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.1138+1927G>T		intron	N/A	NP_001136430.1
	FBXO15	NM_152676.3		c.910+1927G>T		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.1138+1927G>T		intron	N/A	ENSP00000393154.2
	FBXO15	ENST00000583443.5	TSL:1	n.*1147+1927G>T		intron	N/A	ENSP00000464177.1
	FBXO15	ENST00000580088.1	TSL:5	c.142+1927G>T		intron	N/A	ENSP00000462117.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56612 AN: 151946 Hom.: 11927 Cov.: 33

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.373 AC: 56705 AN: 152066 Hom.: 11964 Cov.: 33 AF XY: 0.371 AC XY: 27592 AN XY: 74328

African (AFR) AF: 0.565 AC: 23434 AN: 41478

American (AMR) AF: 0.417 AC: 6375 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3468

East Asian (EAS) AF: 0.432 AC: 2233 AN: 5170

South Asian (SAS) AF: 0.262 AC: 1259 AN: 4814

European-Finnish (FIN) AF: 0.182 AC: 1921 AN: 10572

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19427 AN: 67958

Other (OTH) AF: 0.353 AC: 747 AN: 2114

Alfa AF: 0.319 Hom.: 24050

Bravo AF: 0.403

Asia WGS AF: 0.347 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		0.045
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: rs9945428; hg19: chr18-71788676;