Genetic Variant FNBP1:p.Arg489His (chr9-129900510-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015033.3(FNBP1):c.1466G>A(p.Arg489His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,591,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R489C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

FNBP1
NM_015033.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

Publications

0 publications found

Variant links:

Genes affected

FNBP1 (HGNC:17069): (formin binding protein 1) The protein encoded by this gene is a member of the formin-binding-protein family. The protein contains an N-terminal Fer/Cdc42-interacting protein 4 (CIP4) homology (FCH) domain followed by a coiled-coil domain, a proline-rich motif, a second coiled-coil domain, a Rho family protein-binding domain (RBD), and a C-terminal SH3 domain. This protein binds sorting nexin 2 (SNX2), tankyrase (TNKS), and dynamin; an interaction between this protein and formin has not been demonstrated yet in human. [provided by RefSeq, Jul 2008]

FNBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18830863).

BS2

High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015033.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FNBP1	NM_015033.3	MANE Select	c.1466G>A	p.Arg489His	missense	Exon 14 of 17	NP_055848.1	Q96RU3-1
FNBP1	NM_001438006.1		c.1550G>A	p.Arg517His	missense	Exon 15 of 18	NP_001424935.1	A0A8V8TQ35
FNBP1	NM_001439039.1		c.1535G>A	p.Arg512His	missense	Exon 14 of 16	NP_001425968.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FNBP1	ENST00000446176.7	TSL:1 MANE Select	c.1466G>A	p.Arg489His	missense	Exon 14 of 17	ENSP00000413625.1	Q96RU3-1
FNBP1	ENST00000699492.1		c.1550G>A	p.Arg517His	missense	Exon 15 of 18	ENSP00000514403.1	A0A8V8TQ35
FNBP1	ENST00000703559.1		c.1466G>A	p.Arg489His	missense	Exon 14 of 16	ENSP00000515375.1	A0A994J3V8

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000531

AC:

AN:

226006

AF XY:

0.0000568

show subpopulations

Gnomad AFR exome

AF:

0.0000727

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000859

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000108

AC:

156

AN:

1439242

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

715582

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32266

American (AMR)

AF:

0.00

AC:

AN:

39984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25344

East Asian (EAS)

AF:

0.00

AC:

AN:

38372

South Asian (SAS)

AF:

0.0000363

AC:

AN:

82736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52800

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5276

European-Non Finnish (NFE)

AF:

0.000136

AC:

150

AN:

1103026

Other (OTH)

AF:

0.0000505

AC:

AN:

59438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000414

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.81

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.9

PhyloP100

2.7

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.0

REVEL

Benign

0.29

Sift

Benign

0.11

Sift4G

Benign

0.068

Polyphen

0.0090

Vest4

0.39

MVP

0.68

MPC

0.46

ClinPred

0.11

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.23

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over