rs10070308

Variant names:

• chr5-107945920-C-T
• rs10070308
• NM_001163315.3:c.1823-64741G>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.1823-64741G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 151,818 control chromosomes in the GnomAD database, including 2,334 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 0.17 (2334 hom., cov: 30)
• Consequence: FBXL17 NM_001163315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL17	NM_001163315.3	c.1823-64741G>A		intron_variant	Intron 7 of 8	ENST00000542267.7	NP_001156787.2
FBXL17	XM_005272048.5	c.1823-64741G>A		intron_variant	Intron 7 of 7		XP_005272105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL17	ENST00000542267.7	c.1823-64741G>A		intron_variant	Intron 7 of 8	1	NM_001163315.3	ENSP00000437464.2
FBXL17	ENST00000496714.2	c.830-64741G>A		intron_variant	Intron 6 of 6	1		ENSP00000418111.2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25747 AN: 151700 Hom.: 2323 Cov.: 30

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.170 AC: 25794 AN: 151818 Hom.: 2334 Cov.: 30 AF XY: 0.172 AC XY: 12726 AN XY: 74176

African (AFR) AF: 0.211 AC: 8737 AN: 41398

American (AMR) AF: 0.145 AC: 2208 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3468

East Asian (EAS) AF: 0.0344 AC: 177 AN: 5148

South Asian (SAS) AF: 0.196 AC: 944 AN: 4814

European-Finnish (FIN) AF: 0.179 AC: 1889 AN: 10538

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10817 AN: 67926

Other (OTH) AF: 0.170 AC: 358 AN: 2110

Alfa AF: 0.171 Hom.: 430

Bravo AF: 0.165

Asia WGS AF: 0.116 AC: 403 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.49
PhyloP100		-0.063
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: rs10070308; hg19: chr5-107281621;