Variant 17-75923216-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001319193.2(FBF1):c.1394C>T(p.Ala465Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,590,368 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00044 ( 1 hom. )

Consequence

FBF1
NM_001319193.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.61

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=0.011391342).

BP6

Variant 17-75923216-G-A is Benign according to our data. Variant chr17-75923216-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2410295.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.1394C>T	p.Ala465Val	missense_variant	14/30	ENST00000636174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBF1	ENST00000636174.2 linkuse as main transcript	c.1394C>T	p.Ala465Val	missense_variant	14/30	5	NM_001319193.2	P2	Q8TES7-6

Frequencies

GnomAD3 genomes

AF:

0.000282

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000264

AC:

AN:

211722

Hom.:

AF XY:

0.000226

AC XY:

AN XY:

114926

show subpopulations

Gnomad AFR exome

AF:

0.000416

Gnomad AMR exome

AF:

0.0000656

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000635

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000105

Gnomad NFE exome

AF:

0.000493

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000439

AC:

631

AN:

1438028

Hom.:

Cov.:

AF XY:

0.000415

AC XY:

296

AN XY:

713246

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.0000728

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000776

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000118

Gnomad4 NFE exome

AF:

0.000542

Gnomad4 OTH exome

AF:

0.000269

GnomAD4 genome

AF:

0.000282

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000426

Hom.:

Bravo

AF:

0.000302

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000246

AC:

ESP6500EA

AF:

0.000478

AC:

ExAC

AF:

0.000216

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

Sep 01, 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

0.073

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.90

Cadd

Benign

0.020

Dann

Benign

0.81

DEOGEN2

Benign

0.026

T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0079

LIST_S2

Benign

0.47

T;T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.075

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

Sift4G

Benign

0.30

T;T;.

Polyphen

0.0020

B;.;B

Vest4

0.026

MVP

0.014

ClinPred

0.0042

GERP RS

-8.4

Varity_R

0.018

gMVP

0.11

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