11-65888042-T-TTTA

Position:

• chr11-65888042-T-TTTA

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4_Supporting PP3 PP5

The NM_004214.5(FIBP):​c.175_176insTAA​(p.His59delinsLeuAsn) variant causes a protein altering change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FIBP NM_004214.5 protein_altering
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.71

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: Nonframeshift variant in NON repetitive region in NM_004214.5. Strenght limited to Supporting due to length of the change: 1aa.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 11-65888042-T-TTTA is Pathogenic according to our data. Variant chr11-65888042-T-TTTA is described in ClinVar as [Pathogenic]. Clinvar id is 254242.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.175_176insTAA	p.His59delinsLeuAsn	protein_altering_variant	2/10	ENST00000357519.9
FIBP	NM_198897.2	c.175_176insTAA	p.His59delinsLeuAsn	protein_altering_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FIBP	ENST00000357519.9	c.175_176insTAA	p.His59delinsLeuAsn	protein_altering_variant	2/10	1	NM_004214.5	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

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

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 15, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886037928; hg19: chr11-65655513;