Genetic Variant FGFBP2:p.Ser136Asn (chr4-15962723-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031950.4(FGFBP2):c.407G>A(p.Ser136Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FGFBP2
NM_031950.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.633

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046577424).

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.407G>A	p.Ser136Asn	missense	Exon 1 of 2	NP_114156.1	Q9BYJ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGFBP2	ENST00000259989.7	TSL:1 MANE Select	c.407G>A	p.Ser136Asn	missense	Exon 1 of 2	ENSP00000259989.6	Q9BYJ0
FGFBP2	ENST00000899354.1		c.407G>A	p.Ser136Asn	missense	Exon 2 of 3	ENSP00000569413.1
FGFBP2	ENST00000509331.1	TSL:2	n.83-2112G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461354

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53012

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111936

Other (OTH)

AF:

0.0000331

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.48

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.00066

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.34

M_CAP

Benign

0.0024

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-0.63

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.48

REVEL

Benign

0.064

Sift

Benign

0.16

Sift4G

Benign

0.34

Polyphen

0.0040

Vest4

0.045

MutPred

0.23

Loss of phosphorylation at S136 (P = 0.02)

MVP

0.081

MPC

0.17

ClinPred

0.26

GERP RS

-1.7

PromoterAI

0.0087

Neutral

(source)

Varity_R

0.061

gMVP

0.097

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over