rs40066

chr5-108180000-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001163315.3(FBXL17):c.1745+6117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,052 control chromosomes in the GnomAD database, including 44,398 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 0.76 (44398 hom., cov: 31)
• Consequence: FBXL17 NM_001163315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315

Genes affected

FBXL17 (HGNC:13615): (F-box and leucine rich repeat protein 17) Members of the F-box protein family, such as FBXL17, 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXL17	NM_001163315.3	c.1745+6117C>T		intron_variant		ENST00000542267.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXL17	ENST00000542267.7	c.1745+6117C>T		intron_variant		1	NM_001163315.3	P1
FBXL17	ENST00000496714.2	c.753+6117C>T		intron_variant		1
FBXL17	ENST00000481160.1	n.401+6117C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115386 AN: 151934 Hom.: 44336 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.760 AC: 115507 AN: 152052 Hom.: 44398 Cov.: 31 AF XY: 0.767 AC XY: 56960 AN XY: 74296

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.735

Alfa AF: 0.722 Hom.: 19547

Bravo AF: 0.757

Asia WGS AF: 0.908 AC: 3155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.44
Dann	Benign	0.50

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: rs40066; hg19: chr5-107515701;