rs786204849

chr11-65885181-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_004214.5(FIBP):c.652C>T(p.Gln218Ter) 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
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 2.60

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_004214.5 Downstream stopcodon found after 21 codons.
• PP5: Variant 11-65885181-G-A is Pathogenic according to our data. Variant chr11-65885181-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 189359.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FIBP	NM_004214.5	c.652C>T	p.Gln218Ter	stop_gained	6/10	ENST00000357519.9
FIBP	NM_198897.2	c.673C>T	p.Gln225Ter	stop_gained	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIBP	ENST00000357519.9	c.652C>T	p.Gln218Ter	stop_gained	6/10	1	NM_004214.5	P4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 149182 Hom.: 0 Cov.: 31 FAILED QC

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: 3 AN: 1048174 Hom.: 0 Cov.: 29 AF XY: 0.00000374 AC XY: 2 AN XY: 534150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000398

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000670 AC: 1 AN: 149182 Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 1 AN XY: 72734

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

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

Submissions by phenotype

Congenital ocular coloboma;C0266617:Congenital anomaly of face;C0426870:Large hands;C0751265:Learning disability;C1849265:Overgrowth;C2243051:Macrocephaly Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

Nov 24, 2014

- -

Tall stature-intellectual disability-renal anomalies syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 15, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.53
Cadd	Pathogenic	39
Dann	Uncertain	0.99
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
MutationTaster	Benign	1.0	A;A;A
Vest4		0.26
GERP RS		5.6

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

LitVar

Other links and lift over

dbSNP: rs786204849; hg19: chr11-65652652;