17-39387196-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032875.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL20	NM_032875.3	MANE Select	c.42+14165A>C		intron	N/A	NP_116264.2
	FBXL20	NM_001370208.3		c.48+14977A>C		intron	N/A	NP_001357137.2
	FBXL20	NM_001370209.3		c.48+14977A>C		intron	N/A	NP_001357138.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL20	ENST00000264658.11	TSL:1 MANE Select	c.42+14165A>C		intron	N/A	ENSP00000264658.6
	FBXL20	ENST00000394294.7	TSL:1	c.42+14165A>C		intron	N/A	ENSP00000377832.3
	FBXL20	ENST00000577399.5	TSL:5	c.48+14977A>C		intron	N/A	ENSP00000462878.1

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

African (AFR) AF: 0.328 AC: 13591 AN: 41436

American (AMR) AF: 0.254 AC: 3865 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1245 AN: 5168

South Asian (SAS) AF: 0.0811 AC: 391 AN: 4822

European-Finnish (FIN) AF: 0.0813 AC: 859 AN: 10570

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11120 AN: 67984

Other (OTH) AF: 0.208 AC: 439 AN: 2108

Alfa AF: 0.176 Hom.: 8874

Bravo AF: 0.236

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.9
DANN	Benign	0.63
PhyloP100		0.28
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: rs7208487; hg19: chr17-37543449;