4-15936271-C-G

Variant names:

• chr4-15936271-C-G
• NM_005130.5:c.362G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005130.5(FGFBP1):​c.362G>C​(p.Arg121Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R121C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FGFBP1 NM_005130.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0880

Genes affected

FGFBP1 (HGNC:19695): (fibroblast growth factor binding protein 1) This gene encodes a secreted fibroblast growth factor carrier protein. The encoded protein plays a critical role in cell proliferation, differentiation and migration by binding to fibroblast growth factors and potentiating their biological effects on target cells. The encoded protein may also play a role in tumor growth as an angiogenic switch molecule, and expression of this gene has been associated with several types of cancer including pancreatic and colorectal adenocarcinoma. A pseudogene of this gene is also located on the short arm of chromosome 4. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFBP1	NM_005130.5	c.362G>C	p.Arg121Pro	missense_variant	Exon 3 of 3	ENST00000382333.2	NP_005121.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFBP1	ENST00000382333.2	c.362G>C	p.Arg121Pro	missense_variant	Exon 3 of 3	3	NM_005130.5	ENSP00000371770.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727232

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.362G>C (p.R121P) alteration is located in exon 2 (coding exon 1) of the FGFBP1 gene. This alteration results from a G to C substitution at nucleotide position 362, causing the arginine (R) at amino acid position 121 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.050
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.15
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.50
MutPred		0.87		Loss of MoRF binding (P = 0.0354);
MVP		0.53
MPC		0.080
ClinPred		0.97	D
GERP RS		1.1
Varity_R		0.93
gMVP		0.77

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: chr4-15937894;