chr5-108122635-C-T

Variant names:

• chr5-108122635-C-T
• rs286810
• NM_001163315.3:c.1745+63482G>A

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+63482G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,978 control chromosomes in the GnomAD database, including 33,548 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 0.65 (33548 hom., cov: 32)
• Consequence: FBXL17 NM_001163315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL17	NM_001163315.3	c.1745+63482G>A		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+63482G>A		intron_variant	Intron 6 of 8	1	NM_001163315.3	ENSP00000437464.2
FBXL17	ENST00000496714.2	c.752+63482G>A		intron_variant	Intron 5 of 6	1		ENSP00000418111.2
FBXL17	ENST00000481160.1	n.401+63482G>A		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99388 AN: 151862 Hom.: 33510 Cov.: 32

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.655 AC: 99478 AN: 151978 Hom.: 33548 Cov.: 32 AF XY: 0.666 AC XY: 49468 AN XY: 74288

African (AFR) AF: 0.495 AC: 20516 AN: 41434

American (AMR) AF: 0.697 AC: 10651 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2314 AN: 3466

East Asian (EAS) AF: 0.924 AC: 4769 AN: 5162

South Asian (SAS) AF: 0.873 AC: 4211 AN: 4822

European-Finnish (FIN) AF: 0.776 AC: 8198 AN: 10560

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.688 AC: 46747 AN: 67958

Other (OTH) AF: 0.652 AC: 1371 AN: 2104

Alfa AF: 0.688 Hom.: 17930

Bravo AF: 0.639

Asia WGS AF: 0.880 AC: 3057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.67
PhyloP100		-1.3
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: rs286810; hg19: chr5-107458336;