Genetic Variant FBXO47:p.Gln209Arg (chr17-38945127-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001008777.3(FBXO47):c.626A>G(p.Gln209Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 1,610,356 control chromosomes in the GnomAD database, including 700,455 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.95 ( 68683 hom., cov: 30)

Exomes 𝑓: 0.93 ( 631772 hom. )

Consequence

FBXO47
NM_001008777.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

FBXO47 (HGNC:31969): (F-box protein 47)

FBXO47 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.728229E-7).

BP6

Variant 17-38945127-T-C is Benign according to our data. Variant chr17-38945127-T-C is described in ClinVar as [Benign]. Clinvar id is 1247558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO47	NM_001008777.3 link	c.626A>G	p.Gln209Arg	missense_variant	Exon 7 of 11	ENST00000378079.3	NP_001008777.2	Q5MNV8
FBXO47	XM_011524865.3 link	c.548A>G	p.Gln183Arg	missense_variant	Exon 7 of 11		XP_011523167.1
FBXO47	XM_011524866.4 link	c.455A>G	p.Gln152Arg	missense_variant	Exon 6 of 10		XP_011523168.1
FBXO47	XM_011524867.3 link	c.626A>G	p.Gln209Arg	missense_variant	Exon 7 of 10		XP_011523169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO47	ENST00000378079.3 link	c.626A>G	p.Gln209Arg	missense_variant	Exon 7 of 11	1	NM_001008777.3	ENSP00000367319.2		Q5MNV8

Frequencies

GnomAD3 genomes

AF:

0.949

AC:

144382

AN:

152070

Hom.:

68622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.986

Gnomad AMI

AF:

0.987

Gnomad AMR

AF:

0.941

Gnomad ASJ

AF:

0.942

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.986

Gnomad FIN

AF:

0.963

Gnomad MID

AF:

0.940

Gnomad NFE

AF:

0.921

Gnomad OTH

AF:

0.936

GnomAD3 exomes

AF:

0.949

AC:

238273

AN:

250958

Hom.:

113253

AF XY:

0.949

AC XY:

128745

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.988

Gnomad AMR exome

AF:

0.958

Gnomad ASJ exome

AF:

0.939

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.985

Gnomad FIN exome

AF:

0.961

Gnomad NFE exome

AF:

0.923

Gnomad OTH exome

AF:

0.938

GnomAD4 exome

AF:

0.930

AC:

1356776

AN:

1458168

Hom.:

631772

Cov.:

AF XY:

0.932

AC XY:

675719

AN XY:

725408

show subpopulations

Gnomad4 AFR exome

AF:

0.989

Gnomad4 AMR exome

AF:

0.956

Gnomad4 ASJ exome

AF:

0.937

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.984

Gnomad4 FIN exome

AF:

0.962

Gnomad4 NFE exome

AF:

0.919

Gnomad4 OTH exome

AF:

0.940

GnomAD4 genome

AF:

0.950

AC:

144503

AN:

152188

Hom.:

68683

Cov.:

AF XY:

0.953

AC XY:

70902

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.986

Gnomad4 AMR

AF:

0.941

Gnomad4 ASJ

AF:

0.942

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.987

Gnomad4 FIN

AF:

0.963

Gnomad4 NFE

AF:

0.921

Gnomad4 OTH

AF:

0.936

Alfa

AF:

0.926

Hom.:

131115

Bravo

AF:

0.949

TwinsUK

AF:

0.923

AC:

3421

ALSPAC

AF:

0.919

AC:

3543

ESP6500AA

AF:

0.985

AC:

4338

ESP6500EA

AF:

0.920

AC:

7914

ExAC

AF:

0.950

AC:

115393

Asia WGS

AF:

0.988

AC:

3438

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30679340) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.0015

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.062

MetaRNN

Benign

5.7e-7

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.67

REVEL

Benign

0.055

Sift

Benign

0.80

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.027

MPC

0.074

ClinPred

0.0019

GERP RS

3.5

Varity_R

0.048

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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