Variant chr1-224114129-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015176.4(FBXO28):c.-1G>C variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.000133 in 1,538,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

FBXO28
NM_015176.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.91

Variant links:

Genes affected

FBXO28 (HGNC:29046): (F-box protein 28) Members of the F-box protein family, such as FBXO28, 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]

FBXO28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-224114129-G-C is Benign according to our data. Variant chr1-224114129-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3040966.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 64 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
FBXO28	NM_015176.4 linkuse as main transcript	c.-1G>C	5_prime_UTR_variant	1/5	ENST00000366862.10
FBXO28	NM_001136115.3 linkuse as main transcript	c.-1G>C	5_prime_UTR_variant	1/4
FBXO28	NR_049764.2 linkuse as main transcript	n.19G>C	non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO28	ENST00000366862.10 linkuse as main transcript	c.-1G>C	5_prime_UTR_variant	1/5	1	NM_015176.4	P1	Q9NVF7-1
FBXO28	ENST00000424254.6 linkuse as main transcript	c.-1G>C	5_prime_UTR_variant	1/4	1			Q9NVF7-2
FBXO28	ENST00000523990.1 linkuse as main transcript	c.-1G>C	5_prime_UTR_variant, NMD_transcript_variant	1/4	2
FBXO28	ENST00000483773.1 linkuse as main transcript		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000420

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000397

AC:

AN:

143662

Hom.:

AF XY:

0.000356

AC XY:

AN XY:

75916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.00171

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000738

Gnomad OTH exome

AF:

0.00146

GnomAD4 exome

AF:

0.000101

AC:

140

AN:

1386428

Hom.:

Cov.:

AF XY:

0.0000952

AC XY:

AN XY:

682538

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00156

Gnomad4 ASJ exome

AF:

0.00160

Gnomad4 EAS exome

AF:

0.0000282

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000196

Gnomad4 OTH exome

AF:

0.000436

GnomAD4 genome

AF:

0.000420

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.000729

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FBXO28-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 10, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over