Variant 17-75917949-G-A 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.2368C>T(p.Arg790Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000748 in 1,603,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

FBF1
NM_001319193.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

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=0.10719022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBF1	NM_001319193.2 linkuse as main transcript	c.2368C>T	p.Arg790Cys	missense_variant	22/30	ENST00000636174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBF1	ENST00000636174.2 linkuse as main transcript	c.2368C>T	p.Arg790Cys	missense_variant	22/30	5	NM_001319193.2	P2	Q8TES7-6
FBF1	ENST00000586717.5 linkuse as main transcript	c.2326C>T	p.Arg776Cys	missense_variant	21/29	5		A2	Q8TES7-1
FBF1	ENST00000319129.10 linkuse as main transcript	c.2200C>T	p.Arg734Cys	missense_variant	17/25	5
FBF1	ENST00000585990.5 linkuse as main transcript	n.2612C>T		non_coding_transcript_exon_variant	20/28	2

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000884

AC:

AN:

237496

Hom.:

AF XY:

0.0000772

AC XY:

AN XY:

129456

show subpopulations

Gnomad AFR exome

AF:

0.0000688

Gnomad AMR exome

AF:

0.000149

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:

0.000112

Gnomad OTH exome

AF:

0.000519

GnomAD4 exome

AF:

0.0000744

AC:

108

AN:

1450944

Hom.:

Cov.:

AF XY:

0.0000652

AC XY:

AN XY:

720330

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000137

Gnomad4 ASJ exome

AF:

0.0000391

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000787

Gnomad4 OTH exome

AF:

0.000184

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000239

AC:

ExAC

AF:

0.000116

AC:

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

Jun 11, 2021

The c.2323C>T (p.R775C) alteration is located in exon 21 (coding exon 20) of the FBF1 gene. This alteration results from a C to T substitution at nucleotide position 2323, causing the arginine (R) at amino acid position 775 to be replaced by a cysteine (C). 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

0.22

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.40

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.39

T;T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.32

Sift4G

Uncertain

0.012

D;D;.

Polyphen

1.0

D;.;D

Vest4

0.48

MVP

0.45

ClinPred

0.33

GERP RS

5.3

Varity_R

0.16

gMVP

0.75

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