Variant 16-87333876-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024735.5(FBXO31):c.1397+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,588,300 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 5 hom., cov: 34)

Exomes 𝑓: 0.0013 ( 28 hom. )

Consequence

FBXO31
NM_024735.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.64

Variant links:

Genes affected

FBXO31 (HGNC:16510): (F-box protein 31) This gene is a member of the F-box family. Members are classified into three classes according to the substrate interaction domain, FBW for WD40 repeats, FBL for leucing-rich repeats, and FBXO for other domains. This protein, classified into the last category because of the lack of a recognizable substrate binding domain, has been proposed to be a component of the SCF ubiquitination complex. It is thought to bind and recruit substrate for ubiquitination and degradation. This protein may have a role in regulating the cell cycle as well as dendrite growth and neuronal migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

FBXO31 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 (BayesDel_noAF=-0.83).

BP6

Variant 16-87333876-G-A is Benign according to our data. Variant chr16-87333876-G-A is described in ClinVar as [Benign]. Clinvar id is 708552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00169 (257/152322) while in subpopulation EAS AF= 0.0377 (195/5172). AF 95% confidence interval is 0.0334. There are 5 homozygotes in gnomad4. There are 151 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO31	NM_024735.5 linkuse as main transcript	c.1397+10C>T		intron_variant		ENST00000311635.12
FBXO31	NM_001282683.2 linkuse as main transcript	c.881+10C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
FBXO31	ENST00000311635.12 linkuse as main transcript	c.1397+10C>T	intron_variant	1	NM_024735.5	P1	Q5XUX0-1
FBXO31	ENST00000618298.6 linkuse as main transcript	c.881+10C>T	intron_variant	5
FBXO31	ENST00000636077.2 linkuse as main transcript	c.1484+10C>T	intron_variant	5
FBXO31	ENST00000565593.1 linkuse as main transcript	c.*103+10C>T	intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

260

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0382

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00310

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00332

AC:

764

AN:

230172

Hom.:

AF XY:

0.00302

AC XY:

376

AN XY:

124668

show subpopulations

Gnomad AFR exome

AF:

0.0000655

Gnomad AMR exome

AF:

0.0000609

Gnomad ASJ exome

AF:

0.000122

Gnomad EAS exome

AF:

0.0378

Gnomad SAS exome

AF:

0.000987

Gnomad FIN exome

AF:

0.00147

Gnomad NFE exome

AF:

0.000224

Gnomad OTH exome

AF:

0.00145

GnomAD4 exome

AF:

0.00129

AC:

1851

AN:

1435978

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

896

AN XY:

711246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000606

Gnomad4 AMR exome

AF:

0.0000700

Gnomad4 ASJ exome

AF:

0.0000411

Gnomad4 EAS exome

AF:

0.0376

Gnomad4 SAS exome

AF:

0.00133

Gnomad4 FIN exome

AF:

0.000965

Gnomad4 NFE exome

AF:

0.0000948

Gnomad4 OTH exome

AF:

0.00152

GnomAD4 genome

AF:

0.00169

AC:

257

AN:

152322

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0377

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00310

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000604

Hom.:

Bravo

AF:

0.00186

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

FBXO31-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 15, 2019

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.35

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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