5-108065750-C-T

Variant names:

• chr5-108065750-C-T
• rs11242661
• NM_001163315.3:c.1746-44749G>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.1746-44749G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,866 control chromosomes in the GnomAD database, including 17,543 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 0.47 (17543 hom., cov: 31)
• Consequence: FBXL17 NM_001163315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL17	NM_001163315.3	c.1746-44749G>A		intron_variant	Intron 6 of 8	ENST00000542267.7	NP_001156787.2
FBXL17	XM_005272048.5	c.1746-44749G>A		intron_variant	Intron 6 of 7		XP_005272105.1
FBXL17	XM_011543574.4	c.1746-44749G>A		intron_variant	Intron 6 of 7		XP_011541876.1
FBXL17	XM_011543575.3	c.1746-44749G>A		intron_variant	Intron 6 of 7		XP_011541877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL17	ENST00000542267.7	c.1746-44749G>A		intron_variant	Intron 6 of 8	1	NM_001163315.3	ENSP00000437464.2
FBXL17	ENST00000496714.2	c.753-44749G>A		intron_variant	Intron 5 of 6	1		ENSP00000418111.2
FBXL17	ENST00000481160.1	n.402-44749G>A		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71982 AN: 151748 Hom.: 17523 Cov.: 31

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.474 AC: 72046 AN: 151866 Hom.: 17543 Cov.: 31 AF XY: 0.478 AC XY: 35486 AN XY: 74198

African (AFR) AF: 0.368 AC: 15248 AN: 41432

American (AMR) AF: 0.581 AC: 8866 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1874 AN: 3468

East Asian (EAS) AF: 0.557 AC: 2864 AN: 5142

South Asian (SAS) AF: 0.418 AC: 2007 AN: 4800

European-Finnish (FIN) AF: 0.538 AC: 5663 AN: 10532

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33865 AN: 67914

Other (OTH) AF: 0.493 AC: 1041 AN: 2112

Alfa AF: 0.489 Hom.: 5462

Bravo AF: 0.478

Asia WGS AF: 0.505 AC: 1759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.80
PhyloP100		-0.013
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: rs11242661; hg19: chr5-107401451; COSMIC: COSV62860331;