rs886037928

Variant names:

• chr11-65888042-T-TTTA
• rs886037928
• NM_004214.5:c.175_176insTAA

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4_Supporting PP3 PP5_Moderate

The NM_004214.5(FIBP):​c.175_176insTAA​(p.His59delinsLeuAsn) variant causes a conservative inframe insertion 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 Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FIBP NM_004214.5 conservative_inframe_insertion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• 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 Likely_pathogenic. Variant got 6 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 [Likely_pathogenic]. Clinvar id is 254242.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIBP	NM_004214.5	c.175_176insTAA	p.His59delinsLeuAsn	conservative_inframe_insertion	Exon 2 of 10	ENST00000357519.9	NP_004205.2
FIBP	NM_198897.2	c.175_176insTAA	p.His59delinsLeuAsn	conservative_inframe_insertion	Exon 2 of 10		NP_942600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIBP	ENST00000357519.9	c.175_176insTAA	p.His59delinsLeuAsn	conservative_inframe_insertion	Exon 2 of 10	1	NM_004214.5	ENSP00000350124.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Tall stature-intellectual disability-renal anomalies syndrome Pathogenic:2

Oct 04, 2024

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

PM4,PM2,PP1,PS3(moderate) -

Sep 15, 2016

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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;