5-107977702-A-G

Position:

• chr5-107977702-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001163315.3(FBXL17):​c.1822+43223T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,178 control chromosomes in the GnomAD database, including 5,099 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 0.25 (5099 hom., cov: 33)
• Consequence: FBXL17 NM_001163315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXL17	NM_001163315.3	c.1822+43223T>C		intron_variant		ENST00000542267.7
FBXL17	XM_005272048.5	c.1822+43223T>C		intron_variant
FBXL17	XM_011543574.4	c.1823-31006T>C		intron_variant
FBXL17	XM_011543575.3	c.1823-19567T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXL17	ENST00000542267.7	c.1822+43223T>C		intron_variant		1	NM_001163315.3	P1
FBXL17	ENST00000496714.2	c.830+43223T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38487 AN: 152060 Hom.: 5089 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.253 AC: 38521 AN: 152178 Hom.: 5099 Cov.: 33 AF XY: 0.253 AC XY: 18794 AN XY: 74382

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.0842

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.248

Alfa AF: 0.274 Hom.: 6449

Bravo AF: 0.246

Asia WGS AF: 0.160 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs10900900; hg19: chr5-107313403; COSMIC: COSV62859966;