5-177090558-A-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_213647.3(FGFR4):c.260A>T(p.Glu87Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000131 in 1,526,758 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 7.3e-7 ( 0 hom. )
Consequence
FGFR4
NM_213647.3 missense
NM_213647.3 missense
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 5.40
Publications
0 publications found
Genes affected
FGFR4 (HGNC:3691): (fibroblast growth factor receptor 4) The protein encoded by this gene is a tyrosine kinase and cell surface receptor for fibroblast growth factors. The encoded protein is involved in the regulation of several pathways, including cell proliferation, cell differentiation, cell migration, lipid metabolism, bile acid biosynthesis, vitamin D metabolism, glucose uptake, and phosphate homeostasis. This protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment, and a cytoplasmic tyrosine kinase domain. The extracellular portion interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. [provided by RefSeq, Aug 2017]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.818
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152050Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152050
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000550 AC: 1AN: 181734 AF XY: 0.0000105 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
181734
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 7.27e-7 AC: 1AN: 1374708Hom.: 0 Cov.: 70 AF XY: 0.00000148 AC XY: 1AN XY: 674442 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1374708
Hom.:
Cov.:
70
AF XY:
AC XY:
1
AN XY:
674442
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30596
American (AMR)
AF:
AC:
0
AN:
30850
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
20240
East Asian (EAS)
AF:
AC:
1
AN:
39004
South Asian (SAS)
AF:
AC:
0
AN:
71240
European-Finnish (FIN)
AF:
AC:
0
AN:
49808
Middle Eastern (MID)
AF:
AC:
0
AN:
5352
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1071064
Other (OTH)
AF:
AC:
0
AN:
56554
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000658 AC: 1AN: 152050Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74264 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152050
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74264
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41394
American (AMR)
AF:
AC:
0
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
1
AN:
5194
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10604
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67986
Other (OTH)
AF:
AC:
0
AN:
2084
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Mar 07, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.260A>T (p.E87V) alteration is located in exon 3 (coding exon 2) of the FGFR4 gene. This alteration results from a A to T substitution at nucleotide position 260, causing the glutamic acid (E) at amino acid position 87 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;T;.;.;D;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T;T;T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;.;.;.;N;.;.;N
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Benign
T;D;T;D;T;D;D;T
Sift4G
Benign
T;D;T;D;T;D;D;T
Polyphen
D;P;.;.;D;.;.;D
Vest4
MutPred
Gain of MoRF binding (P = 0.0412);Gain of MoRF binding (P = 0.0412);Gain of MoRF binding (P = 0.0412);Gain of MoRF binding (P = 0.0412);Gain of MoRF binding (P = 0.0412);Gain of MoRF binding (P = 0.0412);Gain of MoRF binding (P = 0.0412);Gain of MoRF binding (P = 0.0412);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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