Variant 17-75920405-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001319193.2(FBF1):c.1699C>T(p.Arg567Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00041 in 1,607,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

FBF1
NM_001319193.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.283

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022842348).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBF1	NM_001319193.2 linkuse as main transcript	c.1699C>T	p.Arg567Trp	missense_variant	18/30	ENST00000636174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBF1	ENST00000636174.2 linkuse as main transcript	c.1699C>T	p.Arg567Trp	missense_variant	18/30	5	NM_001319193.2	P2	Q8TES7-6

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000341

AC:

AN:

234576

Hom.:

AF XY:

0.000337

AC XY:

AN XY:

127648

show subpopulations

Gnomad AFR exome

AF:

0.000144

Gnomad AMR exome

AF:

0.000662

Gnomad ASJ exome

AF:

0.000733

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000693

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000435

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.000425

AC:

618

AN:

1455168

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

313

AN XY:

723140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000708

Gnomad4 ASJ exome

AF:

0.000734

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000707

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.000480

Gnomad4 OTH exome

AF:

0.000466

GnomAD4 genome

AF:

0.000269

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000239

Hom.:

Bravo

AF:

0.000363

ESP6500AA

AF:

0.000513

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.000323

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Sep 15, 2021

The c.1654C>T (p.R552W) alteration is located in exon 17 (coding exon 16) of the FBF1 gene. This alteration results from a C to T substitution at nucleotide position 1654, causing the arginine (R) at amino acid position 552 to be replaced by a tryptophan (W). 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

0.066

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.64

Cadd

Benign

8.5

Dann

Benign

0.66

DEOGEN2

Benign

0.066

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.023

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.20

Sift4G

Benign

0.18

T;T;.

Polyphen

0.0040

B;.;B

Vest4

0.10

MVP

0.072

ClinPred

0.015

GERP RS

0.54

Varity_R

0.086

gMVP

0.26

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