11-65884649-G-T

Position:

• chr11-65884649-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004214.5(FIBP):​c.827C>A​(p.Ser276Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FIBP NM_004214.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.55

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FIBP	NM_004214.5	c.827C>A	p.Ser276Tyr	missense_variant	8/10	ENST00000357519.9
FIBP	NM_198897.2	c.848C>A	p.Ser283Tyr	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIBP	ENST00000357519.9	c.827C>A	p.Ser276Tyr	missense_variant	8/10	1	NM_004214.5	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Jan 27, 2021

The c.848C>A (p.S283Y) alteration is located in exon 8 (coding exon 8) of the FIBP gene. This alteration results from a C to A substitution at nucleotide position 848, causing the serine (S) at amino acid position 283 to be replaced by a tyrosine (Y). The in silico prediction for the p.S283Y alteration is inconclusive. 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Benign	0.088	N
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.29
Sift	Benign	0.077	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.94
MutPred		0.71		Gain of helix (P = 0.0496);.;.;
MVP		0.30
MPC		1.7
ClinPred		0.96	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65652120;