Variant 4-15962951-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_031950.4(FGFBP2):c.179G>C(p.Arg60Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,609,984 control chromosomes in the GnomAD database, including 1 homozygotes. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000045 ( 1 hom. )

Consequence

FGFBP2
NM_031950.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35

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]

FGFBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFBP2	NM_031950.4 linkuse as main transcript	c.179G>C	p.Arg60Pro	missense_variant	1/2	ENST00000259989.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFBP2	ENST00000259989.7 linkuse as main transcript	c.179G>C	p.Arg60Pro	missense_variant	1/2	1	NM_031950.4	P1
FGFBP2	ENST00000509331.1 linkuse as main transcript	n.83-2340G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

247792

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

134122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000621

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000453

AC:

AN:

1457776

Hom.:

Cov.:

AF XY:

0.0000455

AC XY:

AN XY:

725064

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:

0.0000549

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2022

The c.179G>C (p.R60P) alteration is located in exon 1 (coding exon 1) of the FGFBP2 gene. This alteration results from a G to C substitution at nucleotide position 179, causing the arginine (R) at amino acid position 60 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

0.92

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.28

Cadd

Benign

Dann

Benign

0.68

DEOGEN2

Benign

0.064

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.40

M_CAP

Benign

0.0078

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.28

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0

Polyphen

0.78

Vest4

0.50

MutPred

0.70

Loss of MoRF binding (P = 0.0247);

MVP

0.18

MPC

0.70

ClinPred

0.58

GERP RS

0.029

Varity_R

0.54

gMVP

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over