chr4-15962465-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031950.4(FGFBP2):​c.665G>T​(p.Arg222Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,402,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R222Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FGFBP2
NM_031950.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.182
Variant links:
Genes affected
FGFBP2 (HGNC:29451): (fibroblast growth factor binding protein 2) This gene encodes a member of the fibroblast growth factor binding protein family. The encoded protein is a serum protein that is selectively secreted by cytotoxic lymphocytes and may be involved in cytotoxic lymphocyte-mediated immunity. An increase in the amount of gene product may be associated with atopic asthma and mild extrinsic asthma.[provided by RefSeq Staff, Oct 2008]

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ACMG classification

Classification made for transcript

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=0.08674696).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FGFBP2NM_031950.4 linkc.665G>T p.Arg222Leu missense_variant Exon 1 of 2 ENST00000259989.7 NP_114156.1 Q9BYJ0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FGFBP2ENST00000259989.7 linkc.665G>T p.Arg222Leu missense_variant Exon 1 of 2 1 NM_031950.4 ENSP00000259989.6 Q9BYJ0
FGFBP2ENST00000509331.1 linkn.83-1854G>T intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000143
AC:
2
AN:
1402498
Hom.:
0
Cov.:
32
AF XY:
0.00000145
AC XY:
1
AN XY:
691036
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
3.7
DANN
Benign
0.73
DEOGEN2
Benign
0.010
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.048
N
LIST_S2
Benign
0.40
T
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.087
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.14
N
PrimateAI
Benign
0.24
T
PROVEAN
Uncertain
-3.2
D
REVEL
Benign
0.066
Sift
Benign
0.15
T
Sift4G
Benign
0.83
T
Polyphen
0.0040
B
Vest4
0.12
MutPred
0.61
Loss of MoRF binding (P = 0.018);
MVP
0.014
MPC
0.21
ClinPred
0.047
T
GERP RS
-5.1
Varity_R
0.062
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr4-15964088; API