Variant 17-75921960-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001319193.2(FBF1):c.1511G>C(p.Arg504Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000322 in 1,551,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FBF1
NM_001319193.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.158

Variant links:

Genes affected

FBF1 (HGNC:24674): (Fas binding factor 1) Involved in apical junction assembly and establishment of epithelial cell polarity. Acts upstream of or within cilium assembly. Located in centriole; centrosome; and spindle pole. Part of ciliary transition fiber. Colocalizes with apical junction complex and keratin filament. [provided by Alliance of Genome Resources, Apr 2022]

FBF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10460606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBF1	NM_001319193.2 linkuse as main transcript	c.1511G>C	p.Arg504Thr	missense_variant	15/30	ENST00000636174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBF1	ENST00000636174.2 linkuse as main transcript	c.1511G>C	p.Arg504Thr	missense_variant	15/30	5	NM_001319193.2	P2	Q8TES7-6

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000637

AC:

AN:

157036

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82948

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000164

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1398978

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689972

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.1466G>C (p.R489T) alteration is located in exon 14 (coding exon 13) of the FBF1 gene. This alteration results from a G to C substitution at nucleotide position 1466, causing the arginine (R) at amino acid position 489 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

Cadd

Benign

1.9

Dann

Benign

0.50

DEOGEN2

Benign

0.042

T;T;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.62

T;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.24

Sift4G

Benign

0.77

T;T;.

Polyphen

0.59

P;.;P

Vest4

0.17

MutPred

0.24

Gain of glycosylation at R490 (P = 0.0023);.;.;

MVP

0.081

ClinPred

0.088

GERP RS

0.99

Varity_R

0.15

gMVP

0.23

Splicing

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