17-75930038-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001319193.2(FBF1):c.238A>G(p.Ile80Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,520,192 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

FBF1
NM_001319193.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.02

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018091857).

BP6

Variant 17-75930038-T-C is Benign according to our data. Variant chr17-75930038-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2255948.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBF1	NM_001319193.2 linkuse as main transcript	c.238A>G	p.Ile80Val	missense_variant	7/30	ENST00000636174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBF1	ENST00000636174.2 linkuse as main transcript	c.238A>G	p.Ile80Val	missense_variant	7/30	5	NM_001319193.2	P2	Q8TES7-6
FBF1	ENST00000586717.5 linkuse as main transcript	c.196A>G	p.Ile66Val	missense_variant	6/29	5		A2	Q8TES7-1
FBF1	ENST00000319129.10 linkuse as main transcript	c.73A>G	p.Ile25Val	missense_variant	2/25	5
FBF1	ENST00000585990.5 linkuse as main transcript	n.316A>G		non_coding_transcript_exon_variant	6/28	2

Frequencies

GnomAD3 genomes

AF:

0.0000353

AC:

AN:

141584

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000527

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000796

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:

0.0000300

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000551

AC:

AN:

181652

Hom.:

AF XY:

0.0000103

AC XY:

AN XY:

96718

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:

0.0000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1378608

Hom.:

Cov.:

AF XY:

0.0000103

AC XY:

AN XY:

681088

show subpopulations

Gnomad4 AFR exome

AF:

0.0000319

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000103

Gnomad4 OTH exome

AF:

0.0000178

GnomAD4 genome

AF:

0.0000353

AC:

AN:

141584

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

67956

show subpopulations

Gnomad4 AFR

AF:

0.0000527

Gnomad4 AMR

AF:

0.0000796

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000300

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

ExAC

AF:

0.0000171

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

Cadd

Benign

0.023

Dann

Benign

0.28

DEOGEN2

Benign

0.027

T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0096

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.27

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

Sift4G

Benign

1.0

T;T;.

Polyphen

0.0010

B;.;B

Vest4

0.059

MutPred

0.12

Gain of phosphorylation at S67 (P = 0.1831);.;.;

MVP

0.040

ClinPred

0.014

GERP RS

-5.9

Varity_R

0.018

gMVP

0.039

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