rs40065

Variant names:

• chr5-108182172-G-A
• rs40065
• NM_001163315.3:c.1745+3945C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-108182172-G-A
• chr5-108182172-G-C
• chr5-108182172-G-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+3945C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,086 control chromosomes in the GnomAD database, including 44,784 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 (44784 hom., cov: 31)
• Consequence: FBXL17 NM_001163315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568
• 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=-0.9).
• 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+3945C>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+3945C>T		intron_variant	Intron 6 of 8	1	NM_001163315.3	ENSP00000437464.2
FBXL17	ENST00000496714.2	c.752+3945C>T		intron_variant	Intron 5 of 6	1		ENSP00000418111.2
FBXL17	ENST00000481160.1	n.401+3945C>T		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115848 AN: 151968 Hom.: 44724 Cov.: 31

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.763 AC: 115968 AN: 152086 Hom.: 44784 Cov.: 31 AF XY: 0.769 AC XY: 57182 AN XY: 74322

African (AFR) AF: 0.860 AC: 35665 AN: 41490

American (AMR) AF: 0.742 AC: 11328 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2295 AN: 3468

East Asian (EAS) AF: 0.931 AC: 4821 AN: 5180

South Asian (SAS) AF: 0.885 AC: 4267 AN: 4820

European-Finnish (FIN) AF: 0.782 AC: 8252 AN: 10556

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

European-Non Finnish (NFE) AF: 0.692 AC: 47055 AN: 67984

Other (OTH) AF: 0.740 AC: 1563 AN: 2112

Alfa AF: 0.719 Hom.: 20269

Bravo AF: 0.761

Asia WGS AF: 0.909 AC: 3158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.1
DANN	Benign	0.64
PhyloP100		0.57
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: rs40065; hg19: chr5-107517873;