Genetic Variant FIBP:p.Gln218Glu (chr11-65885181-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004214.5(FIBP):c.652C>G(p.Gln218Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000954 in 1,048,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 9.5e-7 ( 0 hom. )

Consequence

FIBP
NM_004214.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.60

Publications

0 publications found

Variant links:

Genes affected

FIBP (HGNC:3705): (FGF1 intracellular binding protein) Acidic fibroblast growth factor is mitogenic for a variety of different cell types and acts by stimulating mitogenesis or inducing morphological changes and differentiation. The FIBP protein is an intracellular protein that binds selectively to acidic fibroblast growth factor (aFGF). It is postulated that FIBP may be involved in the mitogenic action of aFGF. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

FIBP Gene-Disease associations (from GenCC):

tall stature-intellectual disability-renal anomalies syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P

FIBP links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07684666).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004214.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIBP	NM_004214.5	MANE Select	c.652C>G	p.Gln218Glu	missense	Exon 6 of 10	NP_004205.2
	FIBP	NM_198897.2		c.673C>G	p.Gln225Glu	missense	Exon 6 of 10	NP_942600.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FIBP	ENST00000357519.9	TSL:1 MANE Select	c.652C>G	p.Gln218Glu	missense	Exon 6 of 10	ENSP00000350124.5
FIBP	ENST00000338369.6	TSL:1	c.673C>G	p.Gln225Glu	missense	Exon 6 of 10	ENSP00000344572.2
FIBP	ENST00000533045.5	TSL:5	c.643C>G	p.Gln215Glu	missense	Exon 6 of 10	ENSP00000434043.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.54e-7

AC:

AN:

1048174

Hom.:

Cov.:

AF XY:

0.00000187

AC XY:

AN XY:

534150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25086

American (AMR)

AF:

0.00

AC:

AN:

42272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21344

East Asian (EAS)

AF:

0.00

AC:

AN:

32692

South Asian (SAS)

AF:

0.00

AC:

AN:

78500

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4784

European-Non Finnish (NFE)

AF:

0.00000133

AC:

AN:

753056

Other (OTH)

AF:

0.00

AC:

AN:

44446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.044

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.79

M_CAP

Benign

0.012

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

2.6

PrimateAI

Benign

0.37

PROVEAN

Benign

0.12

REVEL

Benign

0.13

Sift

Benign

0.73

Sift4G

Benign

1.0

Polyphen

0.069

Vest4

0.12

MutPred

0.37

Gain of loop (P = 0.1069)

MVP

0.29

MPC

0.62

ClinPred

0.27

GERP RS

5.6

Varity_R

0.14

gMVP

0.16

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over