Genetic Variant FGF11:p.Arg33His (chr17-7439718-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_004112.4(FGF11):c.98G>A(p.Arg33His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,420,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R33C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

FGF11
NM_004112.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.76

Publications

0 publications found

Variant links:

Genes affected

FGF11 (HGNC:3667): (fibroblast growth factor 11) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. The function of this gene has not yet been determined. The expression pattern of the mouse homolog implies a role in nervous system development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

FGF11 links:

ENSG00000272884 (HGNC:):

ENSG00000272884 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2677214).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004112.4. 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
	FGF11	NM_004112.4	MANE Select	c.98G>A	p.Arg33His	missense	Exon 1 of 5	NP_004103.1	Q92914
	FGF11	NR_130156.2		n.233+1188G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGF11	ENST00000293829.9	TSL:1 MANE Select	c.98G>A	p.Arg33His	missense	Exon 1 of 5	ENSP00000293829.4	Q92914
FGF11	ENST00000575235.5	TSL:1	c.-180+1188G>A		intron	N/A	ENSP00000459746.1	I3L4N4
ENSG00000272884	ENST00000575331.1	TSL:1	n.213G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000110

AC:

AN:

181312

AF XY:

0.00000987

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000715

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000282

AC:

AN:

1420168

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

705056

show subpopulations

African (AFR)

AF:

0.0000334

AC:

AN:

29914

American (AMR)

AF:

0.0000511

AC:

AN:

39156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24920

East Asian (EAS)

AF:

0.00

AC:

AN:

35526

South Asian (SAS)

AF:

0.00

AC:

AN:

81236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

9.12e-7

AC:

AN:

1096126

Other (OTH)

AF:

0.00

AC:

AN:

58454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.78

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.0

PhyloP100

2.8

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.60

REVEL

Benign

0.23

Sift

Benign

0.13

Sift4G

Uncertain

0.035

Polyphen

0.92

Vest4

0.20

MutPred

0.34

Gain of sheet (P = 0.0344)

MVP

0.80

MPC

2.1

ClinPred

0.71

GERP RS

4.0

PromoterAI

0.026

Neutral

(source)

Varity_R

0.070

gMVP

0.32

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

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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