rs9945428

chr18-74121441-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO15	NM_001142958.2	c.1138+1927G>T		intron_variant		ENST00000419743.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO15	ENST00000419743.7	c.1138+1927G>T		intron_variant		2	NM_001142958.2	P1

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

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.353

Alfa AF: 0.306 Hom.: 9761

Bravo AF: 0.403

Asia WGS AF: 0.347 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.1
Dann	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs9945428; hg19: chr18-71788676;