rs112278577

Variant names:

• chr4-15962465-C-A
• rs112278577
• NM_031950.4:c.665G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-15962465-C-A
• chr4-15962465-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 15/22 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08674696).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031950.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFBP2	NM_031950.4	MANE Select	c.665G>T	p.Arg222Leu	missense	Exon 1 of 2	NP_114156.1	Q9BYJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFBP2	ENST00000259989.7	TSL:1 MANE Select	c.665G>T	p.Arg222Leu	missense	Exon 1 of 2	ENSP00000259989.6	Q9BYJ0
	FGFBP2	ENST00000899354.1		c.665G>T	p.Arg222Leu	missense	Exon 2 of 3	ENSP00000569413.1
	FGFBP2	ENST00000509331.1	TSL:2	n.83-1854G>T		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 36688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21844

East Asian (EAS) AF: 0.00 AC: 0 AN: 39170

South Asian (SAS) AF: 0.00 AC: 0 AN: 77010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5452

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1081940

Other (OTH) AF: 0.00 AC: 0 AN: 57680

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.18
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
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs112278577; hg19: chr4-15964088;