NM_012179.4:c.122+272T>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012179.4(FBXO7):c.122+272T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,610,858 control chromosomes in the GnomAD database, including 33,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2743 hom., cov: 33)

Exomes 𝑓: 0.20 ( 31069 hom. )

Consequence

FBXO7
NM_012179.4 intron

Scores

Splicing: ADA: 0.00005058

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.301

Variant links:

Genes affected

FBXO7 (HGNC:13586): (F-box protein 7) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class and it may play a role in regulation of hematopoiesis. Alternatively spliced transcript variants of this gene have been identified with the full-length natures of only some variants being determined. [provided by RefSeq, Jul 2008]

FBXO7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020529926).

BP6

Variant 22-32475396-T-G is Benign according to our data. Variant chr22-32475396-T-G is described in ClinVar as [Benign]. Clinvar id is 518326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-32475396-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO7	NM_012179.4 link	c.122+272T>G		intron_variant	Intron 1 of 8	ENST00000266087.12	NP_036311.3	Q9Y3I1-1
FBXO7	NM_001033024.2 link	c.35T>G	p.Leu12Arg	missense_variant, splice_region_variant	Exon 1 of 9		NP_001028196.1	Q9Y3I1-2
FBXO7	NM_001257990.2 link	c.-223T>G		splice_region_variant	Exon 1 of 9		NP_001244919.1	Q9Y3I1-3
FBXO7	NM_001257990.2 link	c.-223T>G		5_prime_UTR_variant	Exon 1 of 9		NP_001244919.1	Q9Y3I1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO7	ENST00000266087.12 link	c.122+272T>G		intron_variant	Intron 1 of 8	1	NM_012179.4	ENSP00000266087.7		Q9Y3I1-1

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28782

AN:

152060

Hom.:

2739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.189

GnomAD3 exomes

AF:

0.190

AC:

45980

AN:

241456

Hom.:

4541

AF XY:

0.189

AC XY:

24980

AN XY:

132122

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.131

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.204

AC:

297767

AN:

1458680

Hom.:

31069

Cov.:

AF XY:

0.203

AC XY:

147070

AN XY:

725690

show subpopulations

Gnomad4 AFR exome

AF:

0.142

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.187

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.200

GnomAD4 genome

AF:

0.189

AC:

28800

AN:

152178

Hom.:

2743

Cov.:

AF XY:

0.190

AC XY:

14107

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.146

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.256

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.235

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.205

Hom.:

5263

Bravo

AF:

0.186

TwinsUK

AF:

0.212

AC:

785

ALSPAC

AF:

0.216

AC:

833

ESP6500AA

AF:

0.148

AC:

537

ESP6500EA

AF:

0.205

AC:

1668

ExAC

AF:

0.184

AC:

22264

Asia WGS

AF:

0.130

AC:

453

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Parkinsonian-pyramidal syndrome

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 28, 2016

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Aug 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.1

DANN

Benign

0.51

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

PROVEAN

Benign

-0.45

REVEL

Benign

0.074

Sift

Benign

0.26

Sift4G

Benign

0.77

Polyphen

0.0010

Vest4

0.035

ClinPred

0.0020

GERP RS

-6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000051

dbscSNV1_RF

Benign

0.0020

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