17-39387196-T-G

Variant names:

• chr17-39387196-T-G
• rs7208487
• NM_032875.3:c.42+14165A>C

Variant summary

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

The NM_032875.3(FBXL20):​c.42+14165A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,988 control chromosomes in the GnomAD database, including 4,020 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 0.21 (4020 hom., cov: 31)
• Consequence: FBXL20 NM_032875.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

Genes affected

FBXL20 (HGNC:24679): (F-box and leucine rich repeat protein 20) Members of the F-box protein family, such as FBXL20, 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL20	NM_032875.3	c.42+14165A>C		intron_variant	Intron 1 of 14	ENST00000264658.11	NP_116264.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL20	ENST00000264658.11	c.42+14165A>C		intron_variant	Intron 1 of 14	1	NM_032875.3	ENSP00000264658.6

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32583 AN: 151870 Hom.: 4025 Cov.: 31

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.0804

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.214 AC: 32598 AN: 151988 Hom.: 4020 Cov.: 31 AF XY: 0.211 AC XY: 15710 AN XY: 74310

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.0811

Gnomad4 FIN AF: 0.0813

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.208

Alfa AF: 0.165 Hom.: 3432

Bravo AF: 0.236

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.9
DANN	Benign	0.63

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: rs7208487; hg19: chr17-37543449;