NM_004214.5:c.1034G>A

Variant names:

• chr11-65884014-C-T
• rs1406342033
• NM_004214.5:c.1034G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004214.5(FIBP):​c.1034G>A​(p.Gly345Asp) 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. 15/22 in silico tools predict a benign 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: 1.17
• Publications: 0 publications found

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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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=0.13964981).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIBP	NM_004214.5	MANE Select	c.1034G>A	p.Gly345Asp	missense	Exon 10 of 10	NP_004205.2
	FIBP	NM_198897.2		c.1055G>A	p.Gly352Asp	missense	Exon 10 of 10	NP_942600.1	O43427-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIBP	ENST00000357519.9	TSL:1 MANE Select	c.1034G>A	p.Gly345Asp	missense	Exon 10 of 10	ENSP00000350124.5	O43427-2
	FIBP	ENST00000338369.6	TSL:1	c.1055G>A	p.Gly352Asp	missense	Exon 10 of 10	ENSP00000344572.2	O43427-1
	FIBP	ENST00000926949.1		c.1040G>A	p.Gly347Asp	missense	Exon 9 of 9	ENSP00000597008.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.2
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.13
Sift	Benign	0.60	T
Sift4G	Benign	0.62	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.51		Gain of solvent accessibility (P = 0.0739)
MVP		0.22
MPC		0.70
ClinPred		0.51	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.055
gMVP		0.59
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

dbSNP: rs1406342033; hg19: chr11-65651485;