chr11-65884400-A-C

Position:

• chr11-65884400-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004214.5(FIBP):​c.996T>G​(p.Asp332Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: FIBP NM_004214.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.957

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37201637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FIBP	NM_004214.5	c.996T>G	p.Asp332Glu	missense_variant	9/10	ENST00000357519.9	NP_004205.2
FIBP	NM_198897.2	c.1017T>G	p.Asp339Glu	missense_variant	9/10		NP_942600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FIBP	ENST00000357519.9	c.996T>G	p.Asp332Glu	missense_variant	9/10	1	NM_004214.5	ENSP00000350124.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.1017T>G (p.D339E) alteration is located in exon 9 (coding exon 9) of the FIBP gene. This alteration results from a T to G substitution at nucleotide position 1017, causing the aspartic acid (D) at amino acid position 339 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.75
DEOGEN2	Benign	0.041	T;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.36	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.81	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.65
MutPred		0.48		Loss of loop (P = 0.0235);.;
MVP		0.20
MPC		0.50
ClinPred		0.073	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.036
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65651871;