Genetic Variant FBXL7:c.127+58454G>A (chr5-15674526-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B.

-12

BP4_StrongBA1

The NM_012304.5(FBXL7):c.127+58454G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,000 control chromosomes in the GnomAD database, including 16,863 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 0.46 ( 16863 hom., cov: 32)

Consequence

FBXL7
NM_012304.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0510

Publications

7 publications found

Variant links:

Genes affected

FBXL7 (HGNC:13604): (F-box and leucine rich repeat protein 7) This gene encodes a member of the F-box protein family which is characterized by a 42-48 amino acid motif, the F-box, which binds to the S-phase kinase-associated protein 1 (Skp1) protein. The F-box proteins constitute one of the four subunits of E3 ubiquitin protein ligases called SCFs (SKP1-Cul1-F-box), which play a role in phosphorylation-dependent ubiquitination of proteins. The F-box proteins are divided into 3 subfamilies based on the other domain in the protein: F-box proteins that also have a WD-40 domain (Fbws subfamily), F-box proteins that also have leucine-rich repeats (Fbls subfamily) and F-box proteins that contain other motifs or lack known protein-interaction domains (Fbxs subfamily). The protein encoded by this gene belongs to the Fbls subfamily. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

FBXL7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL7	NM_012304.5 link	c.127+58454G>A		intron_variant	Intron 2 of 3	ENST00000504595.2	NP_036436.1	Q9UJT9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL7	ENST00000504595.2 link	c.127+58454G>A		intron_variant	Intron 2 of 3	1	NM_012304.5	ENSP00000423630.1		Q9UJT9-1
FBXL7	ENST00000510662.1 link	c.-15+58454G>A		intron_variant	Intron 2 of 3	1		ENSP00000425184.1		Q9UJT9-2

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70397

AN:

151882

Hom.:

16833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.581

Gnomad AMI

AF:

0.352

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.581

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.462

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

GnomAD4 genome

AF:

0.464

AC:

70473

AN:

152000

Hom.:

16863

Cov.:

AF XY:

0.458

AC XY:

34068

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.582

AC:

24122

AN:

41466

American (AMR)

AF:

0.414

AC:

6322

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

1421

AN:

3468

East Asian (EAS)

AF:

0.581

AC:

2995

AN:

5154

South Asian (SAS)

AF:

0.388

AC:

1869

AN:

4818

European-Finnish (FIN)

AF:

0.382

AC:

4024

AN:

10538

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.416

AC:

28292

AN:

67964

Other (OTH)

AF:

0.457

AC:

966

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1919

3839

5758

7678

9597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

628

1256

1884

2512

3140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.429

Hom.:

45119

Bravo

AF:

0.472

Asia WGS

AF:

0.477

AC:

1655

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.7

(source)

DANN

Benign

0.51

PhyloP100

0.051

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over