18-74107551-G-T

Variant names:

• chr18-74107551-G-T
• rs1113144
• NM_001142958.2:c.1138+15817C>A

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+15817C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,900 control chromosomes in the GnomAD database, including 7,814 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 0.26 (7814 hom., cov: 32)
• Consequence: FBXO15 NM_001142958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.753
• Publications: 7 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO15	NM_001142958.2	c.1138+15817C>A		intron_variant	Intron 8 of 9	ENST00000419743.7	NP_001136430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO15	ENST00000419743.7	c.1138+15817C>A		intron_variant	Intron 8 of 9	2	NM_001142958.2	ENSP00000393154.2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40024 AN: 151782 Hom.: 7780 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.264 AC: 40112 AN: 151900 Hom.: 7814 Cov.: 32 AF XY: 0.263 AC XY: 19505 AN XY: 74272

African (AFR) AF: 0.538 AC: 22240 AN: 41360

American (AMR) AF: 0.296 AC: 4510 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3466

East Asian (EAS) AF: 0.272 AC: 1405 AN: 5164

South Asian (SAS) AF: 0.135 AC: 648 AN: 4814

European-Finnish (FIN) AF: 0.0706 AC: 747 AN: 10576

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9322 AN: 67942

Other (OTH) AF: 0.237 AC: 501 AN: 2112

Alfa AF: 0.138 Hom.: 1052

Bravo AF: 0.298

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.26
PhyloP100		-0.75
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: rs1113144; hg19: chr18-71774786;