Genetic Variant NM_012157.5:c.*2182T>C (chr3-33387790-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012157.5(FBXL2):c.*2182T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,046 control chromosomes in the GnomAD database, including 11,560 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 0.38 ( 11546 hom., cov: 31)

Exomes 𝑓: 0.38 ( 14 hom. )

Consequence

FBXL2
NM_012157.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.81

Publications

2 publications found

Variant links:

Genes affected

FBXL2 (HGNC:13598): (F-box and leucine rich repeat protein 2) 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 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 Fbls class and, in addition to an F-box, contains 12 tandem leucine-rich repeats. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

FBXL2 links:

Genome browser will be placed here

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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL2	NM_012157.5 link	c.*2182T>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000484457.6	NP_036289.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL2	ENST00000484457.6 link	c.*2182T>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_012157.5	ENSP00000417601.1
FBXL2	ENST00000463736.5 link	n.1214+2062T>C		intron_variant	Intron 12 of 12	2

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58335

AN:

151768

Hom.:

11519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.411

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.392

GnomAD4 exome

AF:

0.380

AC:

AN:

158

Hom.:

Cov.:

AF XY:

0.405

AC XY:

AN XY:

116

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.343

AC:

AN:

140

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.541

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.385

AC:

58406

AN:

151888

Hom.:

11546

Cov.:

AF XY:

0.385

AC XY:

28574

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.410

AC:

16997

AN:

41418

American (AMR)

AF:

0.450

AC:

6868

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

1421

AN:

3466

East Asian (EAS)

AF:

0.477

AC:

2457

AN:

5146

South Asian (SAS)

AF:

0.346

AC:

1664

AN:

4814

European-Finnish (FIN)

AF:

0.345

AC:

3634

AN:

10534

Middle Eastern (MID)

AF:

0.452

AC:

131

AN:

290

European-Non Finnish (NFE)

AF:

0.355

AC:

24097

AN:

67936

Other (OTH)

AF:

0.397

AC:

837

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1771

3543

5314

7086

8857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.366

Hom.:

14515

Bravo

AF:

0.399

Asia WGS

AF:

0.450

AC:

1564

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.9

(source)

DANN

Benign

0.32

PhyloP100

-1.8

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