rs786204849

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_004214.5(FIBP):c.652C>T(p.Gln218*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,048,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FIBP
NM_004214.5 stop_gained

Scores

Clinical Significance

Pathogenic/Likely pathogenic no assertion criteria provided P:2

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 11-65885181-G-A is Pathogenic according to our data. Variant chr11-65885181-G-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 189359.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIBP	NM_004214.5 link	c.652C>T	p.Gln218*	stop_gained	Exon 6 of 10	ENST00000357519.9	NP_004205.2	O43427-2
FIBP	NM_198897.2 link	c.673C>T	p.Gln225*	stop_gained	Exon 6 of 10		NP_942600.1	O43427-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIBP	ENST00000357519.9 link	c.652C>T	p.Gln218*	stop_gained	Exon 6 of 10	1	NM_004214.5	ENSP00000350124.5		O43427-2

Frequencies

GnomAD3 genomes

AF:

0.00000670

AC:

AN:

149182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1048174

Hom.:

Cov.:

AF XY:

0.00000374

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:

0.00000398

AC:

AN:

753056

Other (OTH)

AF:

0.00

AC:

AN:

44446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000670

AC:

AN:

149182

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72734

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40458

American (AMR)

AF:

0.00

AC:

AN:

14954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3444

East Asian (EAS)

AF:

0.00

AC:

AN:

4974

South Asian (SAS)

AF:

0.00

AC:

AN:

4620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67354

Other (OTH)

AF:

0.00

AC:

AN:

2042

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Congenital ocular coloboma;C0266617:Congenital anomaly of face;C0426870:Large hands;C0751265:Learning disability;C1849265:Overgrowth;C2243051:Macrocephaly

Pathogenic:1

Nov 24, 2014

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

Tall stature-intellectual disability-renal anomalies syndrome

Pathogenic:1

Sep 15, 2016

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.53

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.95

PhyloP100

2.6

Vest4

0.26

GERP RS

5.6

Mutation Taster

=5/195

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over