11-65883991-G-T

Variant names:

• chr11-65883991-G-T
• NM_004214.5:c.1057C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004214.5(FIBP):​c.1057C>A​(p.Arg353Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FIBP NM_004214.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82

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]

CTSW (HGNC:2546): (cathepsin W) The protein encoded by this gene, a member of the peptidase C1 family, is a cysteine proteinase that may have a specific function in the mechanism or regulation of T-cell cytolytic activity. The encoded protein is found associated with the membrane inside the endoplasmic reticulum of natural killer and cytotoxic T-cells. Expression of this gene is up-regulated by interleukin-2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15162426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIBP	NM_004214.5	c.1057C>A	p.Arg353Ser	missense_variant	Exon 10 of 10	ENST00000357519.9	NP_004205.2
FIBP	NM_198897.2	c.1078C>A	p.Arg360Ser	missense_variant	Exon 10 of 10		NP_942600.1
CTSW	NM_001335.4	c.*373G>T		downstream_gene_variant		ENST00000307886.8	NP_001326.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIBP	ENST00000357519.9	c.1057C>A	p.Arg353Ser	missense_variant	Exon 10 of 10	1	NM_004214.5	ENSP00000350124.5
CTSW	ENST00000307886.8	c.*373G>T		downstream_gene_variant		1	NM_001335.4	ENSP00000311300.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461614 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727094

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T
Eigen	Benign	0.027
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.094
Sift	Pathogenic	0.0	D
Polyphen		0.0060	B
Vest4		0.23
MutPred		0.10		Gain of solvent accessibility (P = 0.0016);
MVP		0.54
ClinPred		0.74	D
GERP RS		3.9

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: chr11-65651462;