rs370619260

Variant names:

• chr11-65884433-C-G
• NM_004214.5:c.963G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-65884433-C-G
• chr11-65884433-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004214.5(FIBP):​c.963G>C​(p.Leu321Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 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: 6.8e-7 (0 hom.)
• Consequence: FIBP NM_004214.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.860

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_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10004288).
• BP7: Synonymous conserved (PhyloP=0.86 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIBP	NM_004214.5	c.963G>C	p.Leu321Leu	synonymous_variant	Exon 9 of 10	ENST00000357519.9	NP_004205.2
FIBP	NM_198897.2	c.984G>C	p.Leu328Leu	synonymous_variant	Exon 9 of 10		NP_942600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIBP	ENST00000357519.9	c.963G>C	p.Leu321Leu	synonymous_variant	Exon 9 of 10	1	NM_004214.5	ENSP00000350124.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

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: 0.0000116

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
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	12
DANN	Benign	0.89
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.081
Sift	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.083
MutPred		0.35		Loss of solvent accessibility (P = 0.0174);
MVP		0.50
ClinPred		0.11	T
GERP RS		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: chr11-65651904;