rs40066

Variant names:

• chr5-108180000-G-A
• rs40066
• NM_001163315.3:c.1745+6117C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FBXL17	NM_001163315.3	c.1745+6117C>T		intron_variant	Intron 6 of 8	ENST00000542267.7	NP_001156787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL17	ENST00000542267.7	c.1745+6117C>T		intron_variant	Intron 6 of 8	1	NM_001163315.3	ENSP00000437464.2
FBXL17	ENST00000496714.2	c.752+6117C>T		intron_variant	Intron 5 of 6	1		ENSP00000418111.2
FBXL17	ENST00000481160.1	n.401+6117C>T		intron_variant	Intron 4 of 4	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

African (AFR) AF: 0.849 AC: 35223 AN: 41480

American (AMR) AF: 0.742 AC: 11314 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2296 AN: 3468

East Asian (EAS) AF: 0.931 AC: 4812 AN: 5168

South Asian (SAS) AF: 0.886 AC: 4271 AN: 4820

European-Finnish (FIN) AF: 0.782 AC: 8271 AN: 10572

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47048 AN: 67972

Other (OTH) AF: 0.735 AC: 1551 AN: 2110

Alfa AF: 0.721 Hom.: 21718

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
PhyloP100		-0.32
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: rs40066; hg19: chr5-107515701;